• developmental neuroscience
• molecular neuroscience
• neuroscience

• FEZ1
• SCOC
• UNC-69
• UNC-76
• axon
• kinesin
• slow axonal transport
• spectrin

• Animals
• Axonal Transport
• Axons/metabolism
• Caenorhabditis elegans/metabolism
• Caenorhabditis elegans Proteins/genetics
• Caenorhabditis elegans Proteins/metabolism
• Kinesins/metabolism
• Spectrin/metabolism

• R35 GM126950 NIGMS NIH HHS
• R01 NS094219 NINDS NIH HHS
• R01 NS118884 NINDS NIH HHS
• R35 GM133573 NIGMS NIH HHS
• R01 NS114400 NINDS NIH HHS
• R01 AG062210 NIA NIH HHS
• R35 GM131744 NIGMS NIH HHS
• R01 NS098817 NINDS NIH HHS

• Arl8/BORC complex
• Rab2
• kinesins
• presynaptic precursor vesicles

• fasciculation and elongation protein zeta-1
• neurological disorder
• neuronal development
• neuronal differentiation
• neuronal networks
• synapse formation
• synaptic function

• DNA-PK
• FEZ1
• HSPA8
• ISG responses

• Adaptor Proteins, Signal Transducing/metabolism
• Animals
• Cell Nucleus/drug effects
• Cell Nucleus/metabolism
• Chlorocebus aethiops
• DNA Viruses/physiology
• DNA-Activated Protein Kinase/metabolism
• Female
• Gene Expression Regulation/drug effects
• HEK293 Cells
• HSC70 Heat-Shock Proteins/metabolism
• Humans
• Immunity, Innate/drug effects
• Interferon Regulatory Factors/metabolism
• Interferons/pharmacology
• Membrane Proteins/metabolism
• Microglia/drug effects
• Microglia/metabolism
• Nerve Tissue Proteins/metabolism
• Phosphorylation/drug effects
• Phosphoserine/metabolism
• Protein Binding/drug effects
• Protein Transport/drug effects
• Vero Cells

• R01 AI165236 NIAID NIH HHS
• R01 AI150559 NIAID NIH HHS
• K22 AI136691 NIAID NIH HHS
• R01 AI150998 NIAID NIH HHS
• R01 GM101975 NIGMS NIH HHS
• P30 AI117943 NIAID NIH HHS

Pancreatic ductal adenocarcinoma (PDAC) is one of the common malignant tumors with high lethal rate and poor prognosis. Dysregulation of many genes have been reported to be involved in the occurrence and development of PDAC. However, as a highly conserved gene in eukaryotes, the role of Fasciculation and Elongation protein Zeta 2 (FEZ2) in pancreatic cancer progression is not clear. In this study, we identified the oncogenic effect of FEZ2 on PDAC. By mining of The Cancer Genome Atlas (TCGA) database, we found that FEZ2 was upregulated in PDAC tissues and FEZ2 expression was negatively regulated by its methylation. Moreover, high expression and low methylation of FEZ2 correlated with poor prognosis in PDAC patients. Besides, we found that FEZ2 could promote PDAC cells proliferation, migration and 5-FU resistance in vitro. Furthermore, Gene pathway enrichment analysis demonstrated a positive correlation between Wnt signaling activation and FEZ2 expression in PDAC patients. Western blot showed that FEZ2 knockdown significantly suppressed β-catenin expression. Collectively, our finding revealed that FEZ2 functioned as a potential oncogene on PDAC progression and migration, and the expression of FEZ2 had guidance value for the treatment and chemotherapy program of PDAC patients.

• Chemotherapy resistance
• FEZ2
• Pancreatic ductal adenocarcinoma
• Prognosis
• Wnt

Elaboration of neuronal processes is an early step in neuronal development. Guidance cues must work closely with intracellular trafficking pathways to direct expanding axons and dendrites to their target neurons during the formation of neuronal networks. However, how such coordination is achieved remains incompletely understood. Here, we characterize an interaction between fasciculation and elongation protein zeta 1 (FEZ1), an adapter involved in synaptic protein transport, and collapsin response mediator protein (CRMP)1, a protein that functions in growth cone guidance, at neuronal growth cones. We show that similar to CRMP1 loss-of-function mutants, FEZ1 deficiency in rat hippocampal neurons causes growth cone collapse and impairs axonal development. Strikingly, FEZ1-deficient neurons also exhibited a reduction in dendritic complexity stronger than that observed in CRMP1-deficient neurons, suggesting that the former could partake in additional developmental signaling pathways. Supporting this, FEZ1 colocalizes with VAMP2 in developing hippocampal neurons and forms a separate complex with deleted in colorectal cancer (DCC) and Syntaxin-1 (Stx1), components of the Netrin-1 signaling pathway that are also involved in regulating axon and dendrite development. Significantly, developing axons and dendrites of FEZ1-deficient neurons fail to respond to Netrin-1 or Netrin-1 and Sema3A treatment, respectively. Taken together, these findings highlight the importance of FEZ1 as a common effector to integrate guidance signaling pathways with intracellular trafficking to mediate axo-dendrite development during neuronal network formation.

• CRMP1
• DCC
• FEZ1
• axon
• dendrite
• development

• dynamic organization
• intracellular organelle network
• molecular machinery
• organelle interaction
• systems modeling

Although muscle development has been widely studied in Drosophila melanogaster there are still many gaps in our knowledge, and it is not known to which extent this knowledge can be transferred to other insects. To help in closing these gaps we participated in a large-scale RNAi screen that used the red flour beetle, Tribolium castaneum, as a screening platform. The effects of systemic RNAi were screened upon double-stranded RNA injections into appropriate muscle-EGFP tester strains. Injections into pupae were followed by the analysis of the late embryonic/early larval muscle patterns, and injections into larvae by the analysis of the adult thoracic muscle patterns. Herein we describe the results of the first-pass screens with pupal and larval injections, which covered ∼8,500 and ∼5,000 genes, respectively, of a total of ∼16,500 genes of the Tribolium genome. Apart from many genes known from Drosophila as regulators of muscle development, a collection of genes previously unconnected to muscle development yielded phenotypes in larval body wall and leg muscles as well as in indirect flight muscles. We then present the main candidates from the pupal injection screen that remained after being processed through a series of verification and selection steps. Further, we discuss why distinct though overlapping sets of genes are revealed by the Drosophila and Tribolium screening approaches.

• RNAi screen
• Tribolium
• muscle development

Fasciculation and elongation zeta/zygin (FEZ) proteins are a family of hub proteins and share many characteristics like high connectivity in interaction networks, they are involved in several cellular processes, evolve slowly and in general have intrinsically disordered regions. In 1985, unc-76 gene was firstly described and involved in axonal growth in C. elegans, and in 1997 Bloom and Horvitz enrolled also the human homologues genes, FEZ1 and FEZ2, in this process. While nematodes possess one gene (unc-76), mammalians have one more copy (FEZ1 and FEZ2). Several animal models have been used to study FEZ family functions like: C. elegans, D. melanogaster, R. novergicus and human cells. Complementation assays were performed and demonstrated the function conservation between paralogues. Human FEZ1 protein is more studied followed by UNC-76 and FEZ2 proteins, respectively. While FEZ1 and UNC-76 shared interaction partners, FEZ2 evolved and increased the number of protein-protein interactions (PPI) with cytoplasmatic partners. FEZ proteins are implicated in intracellular transport, acting as bivalent cargo transport adaptors in kinesin-mediated movement. Especially in light of this cellular function, this family of proteins has been involved in several processes like neuronal development, neurological disorders, viral infection and autophagy. However, nuclear functions of FEZ proteins have been explored as well, due to high content of PPI with nuclear proteins, correlating FEZ1 expression to Sox2 and Hoxb4 gene regulation and retinoic acid signaling. These recent findings open new avenue to study FEZ proteins functions and its involvement in already described processes. This review intends to reunite aspects of evolution, structure, interaction partners and function of FEZ proteins and correlate them to physiological and pathological processes.

• Hub
• Intrinsically disordered
• FEZ
• Protein-protein interaction
• Neuronal development
• Retinoic acid signaling
• Interactomics

• ARF6
• JIP3
• KLC
• activation
• cargo
• kinesin
• kinesin-1
• molecular
• motor
• regulation

• Amino Acid Sequence
• Animals
• Binding Sites
• Conserved Sequence
• Crystallography, X-Ray
• Humans
• Kinesins/chemistry
• Kinesins/metabolism
• Models, Molecular
• Nerve Tissue Proteins/chemistry
• Nerve Tissue Proteins/metabolism
• Protein Binding
• Protein Conformation

• FC001209 Arthritis Research UK
• FC001209 Wellcome Trust
• Biotechnology and Biological Sciences Research Council
• FC001209 Cancer Research UK
• Wellcome Trust
• 204576/Z/16/Z Wellcome Trust
• 094232/Z/10/Z Wellcome Trust
• FC001209 Medical Research Council

• Humans
• Nerve Tissue Proteins/metabolism
• Nervous System Diseases/metabolism
• Nervous System Diseases/physiopathology
• Neuronal Plasticity
• Signal Transduction
• Synapses/physiology

• Wellcome Trust
• MR/K004603/1 Medical Research Council

We investigate the role of axonal transport in regulating neuronal mitochondrial density. We show that the density of mitochondria in the touch receptor neuron (TRN) of adult Caenorhabditis elegans is constant. Mitochondrial density and transport are controlled both by the Kinesin heavy chain and the Dynein-Dynactin complex. However, unlike in other models, the presence of mitochondria in C. elegans TRNs depends on a Kinesin light chain as well. Mutants in the three C. elegans miro genes do not alter mitochondrial density in the TRNs. Mutants in the Kinesin-1 associated proteins, UNC-16/JIP3 and UNC-76/FEZ1, show increased mitochondrial density and also have elevated levels of both the Kinesin Heavy and Light Chains in neurons. Genetic analyses suggest that, the increased mitochondrial density at the distal end of the neuronal process in unc-16 and unc-76 depends partly on Dynein. We observe a net anterograde bias in the ratio of anterograde to retrograde mitochondrial flux in the neuronal processes of unc-16 and unc-76, likely due to both increased Kinesin-1 and decreased Dynein in the neuronal processes. Our study shows that UNC-16 and UNC-76 indirectly limit mitochondrial density in the neuronal process by maintaining a balance in anterograde and retrograde mitochondrial axonal transport.

• Drosophila
• Khc-73
• Kinesin-2α
• Rab4
• axonal transport
• synapse
• ventral ganglion

New mosquito control strategies are vitally needed to address established arthropod-borne infectious diseases such as dengue and yellow fever and emerging diseases such as Zika and chikungunya, all of which are transmitted by the disease vector mosquito Aedes aegypti. In this investigation, Saccharomyces cerevisiae (baker’s yeast) was engineered to produce short hairpin RNAs (shRNAs) corresponding to the Aedes aegypti orthologs of fasciculation and elongation protein zeta 2 (fez2) and leukocyte receptor cluster (lrc) member, two genes identified in a recent screen for A. aegypti larval lethal genes. Feeding A. aegypti with the engineered yeasts resulted in silenced target gene expression, disrupted neural development, and highly significant larval mortality. Larvicidal activities were retained following heat inactivation and drying of the yeast into tabular formulations that induced >95% mortality and were found to attract adult females to oviposit. These ready-to-use inactivated yeast interfering RNA tablets may one day facilitate the seamless integration of this new class of lure-and-kill species-specific biorational mosquito larvicides into integrated mosquito control programs.

• Drosophila
• axon outgrowth
• dendrite outgrowth
• kinesin-1
• microtubules

• Axonal transport
• KIF5
• KLC
• Kinesin
• Kinesin-1

• Axonal transport
• Drosophila
• MAPK signaling
• Motoneuron
• Neuromuscular junction
• RSK
• Synapse

Synaptic vesicles (SVs) fuse at active zones (AZs) covered by a protein scaffold, at Drosophila synapses comprised of ELKS family member Bruchpilot (BRP) and RIM-binding protein (RBP). We here demonstrate axonal co-transport of BRP and RBP using intravital live imaging, with both proteins co-accumulating in axonal aggregates of several transport mutants. RBP, via its C-terminal Src-homology 3 (SH3) domains, binds Aplip1/JIP1, a transport adaptor involved in kinesin-dependent SV transport. We show in atomic detail that RBP C-terminal SH3 domains bind a proline-rich (PxxP) motif of Aplip1/JIP1 with submicromolar affinity. Pointmutating this PxxP motif provoked formation of ectopic AZ-like structures at axonal membranes. Direct interactions between AZ proteins and transport adaptors seem to provide complex avidity and shield synaptic interaction surfaces of pre-assembled scaffold protein transport complexes, thus, favouring physiological synaptic AZ assembly over premature assembly at axonal membranes.

DOI:http://dx.doi.org/10.7554/eLife.06935.001

To pass on information, the neurons that make up the nervous system connect at structures known as synapses. Chemical messengers called neurotransmitters are released from one neuron, and travel across the synapse to trigger a response in the neighbouring cell. The formation of new synapses plays an important role in learning and memory, but many aspects of this process are not well understood.

In a specific region of the synapse called the active zone, a scaffold of proteins helps to release the neurotransmitters. These proteins are made in the cell body of the neuron, and are then transported to the end of the long, thin axons that protrude from the cell body. This presents a challenge for the cell, because the components of the active zone scaffold must be correctly targeted to the synapse at the end of the axon, ensuring the active zone scaffold assembles only at its proper location.

Siebert, Böhme et al. studied how some of the proteins that are found in the active zone scaffold of the fruit fly Drosophila are transported along axons. Labelling the proteins with fluorescent markers allowed their movement to be examined under a microscope in living Drosophila larvae. The results showed that two of the proteins—known as BRP and RBP—are transported along the axons together. Further investigation revealed that a transport adaptor protein called Aplip1, which binds to RBP, is required for this movement. Siebert, Böhme et al. established the structure of the part of RBP where this interaction occurs, and found that mutating this region causes premature active zone scaffold assembly in the axonal part of the neuron. The interaction between RBP and Aplip1 is very strong, and this helps to prevent the scaffold assembling before it has reached the correct part of the neuron. Exactly how the transport adaptor and active zone protein are separated once they reach their final destination (the synapse) remains to be discovered.

DOI:http://dx.doi.org/10.7554/eLife.06935.002

• AZ scaffold proteins
• D. melanogaster
• active zone
• axonal transport
• neuroscience
• synapses
• transport adaptor

• SCHIP-1
• ankyrin G
• axon initial segment
• protein kinase CK2

• DOA Translation elongation factor EF1γ, EF1γ
• Darkener of apricot
• Drosophila melanogaster S2 cells
• Organelle transport

• Adaptor Proteins, Signal Transducing/chemistry
• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Amino Acid Sequence
• Binding Sites/genetics
• Biological Transport
• Carrier Proteins/chemistry
• Carrier Proteins/genetics
• Carrier Proteins/metabolism
• Humans
• Kinesins
• Magnetic Resonance Spectroscopy
• Membrane Proteins/chemistry
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• Microtubule-Associated Proteins/metabolism
• Models, Molecular
• Molecular Sequence Data
• Nerve Tissue Proteins/chemistry
• Nerve Tissue Proteins/genetics
• Nerve Tissue Proteins/metabolism
• Protein Binding
• Protein Multimerization
• Protein Structure, Tertiary
• Recombinant Proteins/chemistry
• Recombinant Proteins/metabolism
• Scattering, Small Angle
• Sequence Homology, Amino Acid
• Two-Hybrid System Techniques
• X-Ray Diffraction

The short coiled coil protein (SCOC) forms a complex with fasciculation and elongation protein zeta 1 (FEZ1). This complex is involved in autophagy regulation. We determined the crystal structure of the coiled coil domain of human SCOC at 2.7 Å resolution. SCOC forms a parallel left handed coiled coil dimer. We observed two distinct dimers in the crystal structure, which shows that SCOC is conformationally flexible. This plasticity is due to the high incidence of polar and charged residues at the core a/d-heptad positions. We prepared two double mutants, where these core residues were mutated to either leucines or valines (E93V/K97L and N125L/N132V). These mutations led to a dramatic increase in stability and change of oligomerisation state. The oligomerisation state of the mutants was characterized by multi-angle laser light scattering and native mass spectrometry measurements. The E93V/K97 mutant forms a trimer and the N125L/N132V mutant is a tetramer. We further demonstrate that SCOC forms a stable homogeneous complex with the coiled coil domain of FEZ1. SCOC dimerization and the SCOC surface residue R117 are important for this interaction.

• Adaptor Proteins, Signal Transducing/chemistry
• Adaptor Proteins, Signal Transducing/metabolism
• Amino Acid Sequence
• Carrier Proteins/chemistry
• Carrier Proteins/genetics
• Carrier Proteins/metabolism
• Cell Line
• Crystallography, X-Ray
• Humans
• Membrane Proteins/chemistry
• Membrane Proteins/genetics
• Membrane Proteins/metabolism
• Models, Molecular
• Molecular Sequence Data
• Mutation
• Nerve Tissue Proteins/chemistry
• Nerve Tissue Proteins/metabolism
• Protein Binding
• Protein Conformation
• Protein Interaction Domains and Motifs
• Protein Transport
• Sequence Alignment

• Wellcome Trust

Formation and normal function of neuronal synapses are intimately dependent on the delivery to and removal of biological materials from synapses by the intracellular transport machinery. Indeed, defects in intracellular transport contribute to the development and aggravation of neurodegenerative disorders. Despite its importance, regulatory mechanisms underlying this machinery remain poorly defined. We recently uncovered a phosphorylation-regulated mechanism that controls FEZ1-mediated Kinesin-1-based delivery of Stx1 into neuronal axons. Using C. elegans as a model organism to investigate transport defects, we show that FEZ1 mutations resulted in abnormal Stx1 aggregation in neuronal cell bodies and axons. This phenomenon closely resembles transport defects observed in neurodegenerative disorders. Importantly, diminished transport due to mutations of FEZ1 and Kinesin-1 were concomitant with increased accumulation of autophagosomes. Here, we discuss the significance of our findings in a broader context in relation to regulation of Kinesin-mediated transport and neurodegenerative disorders.

• FEZ1
• Kinesin
• Munc18
• SNARE
• Syntaxin
• autophagy
• axonal transport
• neurodegeneration
• synapse
• transport defects

Amyloid precursor protein (APP) vesicle movement by kinesin-1 and cytoplasmic dynein exhibits kinesin-1–dependent velocity. Our data also suggest that kinesin-1 and cytoplasmic dynein motors assemble in stable mixtures on APP vesicles and that their direction and velocity are controlled at least in part by dynein IC.

Bidirectional axonal transport driven by kinesin and dynein along microtubules is critical to neuronal viability and function. To evaluate axonal transport mechanisms, we developed a high-resolution imaging system to track the movement of amyloid precursor protein (APP) vesicles in Drosophila segmental nerve axons. Computational analyses of a large number of moving vesicles in defined genetic backgrounds with partial reduction or overexpression of motor proteins enabled us to test with high precision existing and new models of motor activity and coordination in vivo. We discovered several previously unknown features of vesicle movement, including a surprising dependence of anterograde APP vesicle movement velocity on the amount of kinesin-1. This finding is largely incompatible with the biophysical properties of kinesin-1 derived from in vitro analyses. Our data also suggest kinesin-1 and cytoplasmic dynein motors assemble in stable mixtures on APP vesicles and their direction and velocity are controlled at least in part by dynein intermediate chain.

• Axonal transport
• Neurodegenerative diseases

• disc1
• fez1
• lithium
• bipolar disorder
• vesicle transport
• motor–cargo assembly

• Animals
• Axonal Transport/drug effects
• Axonal Transport/physiology
• COS Cells
• Cells, Cultured
• Chlorocebus aethiops
• Female
• Lithium Compounds/pharmacology
• Mice
• Mice, Inbred C57BL
• Microtubules/drug effects
• Microtubules/physiology
• Nerve Tissue Proteins/physiology
• Neurons/cytology
• Neurons/drug effects
• Neurons/metabolism
• Organelles/drug effects
• Organelles/physiology
• Pregnancy
• Primary Cell Culture/methods
• Signal Transduction/drug effects
• Signal Transduction/physiology
• Synaptic Vesicles/drug effects
• Synaptic Vesicles/metabolism

• R01 MH069853-05 NIMH NIH HHS
• MH-069853 NIMH NIH HHS
• R01 MH069853-01A1 NIMH NIH HHS
• R01 MH069853-08 NIMH NIH HHS
• R01 MH069853-07 NIMH NIH HHS
• R21 MH085226 NIMH NIH HHS
• P20 MH084018-03 NIMH NIH HHS
• P20 MH084018-02 NIMH NIH HHS
• MH-084018 NIMH NIH HHS
• R01 MH069853-02 NIMH NIH HHS
• R01 MH069853-06 NIMH NIH HHS
• P20 MH084018-02S1 NIMH NIH HHS
• RC1 MH088753 NIMH NIH HHS
• R01 MH069853-03 NIMH NIH HHS
• P41 RR001192 NCRR NIH HHS
• MH-088753 NIMH NIH HHS
• R21 MH085226-02 NIMH NIH HHS
• R01 MH069853 NIMH NIH HHS
• R21 MH085226-01A2 NIMH NIH HHS
• P20 MH084018-01 NIMH NIH HHS
• R01 MH069853-04 NIMH NIH HHS
• MH-085226 NIMH NIH HHS
• R01 MH069853-09 NIMH NIH HHS
• P20 MH084018 NIMH NIH HHS

• mitochondria
• axonal transport
• docking
• synaptic plasticity
• kinesin
• motor adaptor
• anterograde transport
• retrograde transport
• stationary mitochondria
• mitochondrial mobility

• Animals
• Axonal Transport/physiology
• Axons/physiology
• Calcium Signaling/physiology
• Cells, Cultured
• Humans
• Mitochondria/metabolism
• Mitochondria/physiology
• Molecular Motor Proteins/physiology
• Synaptic Transmission/physiology

• ZIA NS003029 Intramural NIH HHS
• ZIA NS003029-04 Intramural NIH HHS

The FEZ (fasciculation and elongation protein zeta) family designation was purposed by Bloom and Horvitz by genetic analysis of C. elegans unc-76. Similar human sequences were identified in the expressed sequence tag database as FEZ1 and FEZ2. The unc-76 function is necessary for normal axon fasciculation and is required for axon-axon interactions. Indeed, the loss of UNC-76 function results in defects in axonal transport. The human FEZ1 protein has been shown to rescue defects caused by unc-76 mutations in nematodes, indicating that both UNC-76 and FEZ1 are evolutionarily conserved in their function. Until today, little is known about FEZ2 protein function.

Using the yeast two-hybrid system we demonstrate here conserved evolutionary features among orthologs and non-conserved features between paralogs of the FEZ family of proteins, by comparing the interactome profiles of the C-terminals of human FEZ1, FEZ2 and UNC-76 from C. elegans. Furthermore, we correlate our data with an analysis of the molecular evolution of the FEZ protein family in the animal kingdom.

We found that FEZ2 interacted with 59 proteins and that of these only 40 interacted with FEZ1. Of the 40 FEZ1 interacting proteins, 36 (90%), also interacted with UNC-76 and none of the 19 FEZ2 specific proteins interacted with FEZ1 or UNC-76. This together with the duplication of unc-76 gene in the ancestral line of chordates suggests that FEZ2 is in the process of acquiring new additional functions. The results provide also an explanation for the dramatic difference between C. elegans and D. melanogaster unc-76 mutants on one hand, which cause serious defects in the nervous system, and the mouse FEZ1 -/- knockout mice on the other, which show no morphological and no strong behavioural phenotype. Likely, the ubiquitously expressed FEZ2 can completely compensate the lack of neuronal FEZ1, since it can interact with all FEZ1 interacting proteins and additional 19 proteins.

• Adaptor Proteins, Signal Transducing/chemistry
• Adaptor Proteins, Signal Transducing/genetics
• Adaptor Proteins, Signal Transducing/metabolism
• Amino Acid Sequence
• Animals
• Caenorhabditis elegans/metabolism
• Caenorhabditis elegans Proteins/metabolism
• Cell Adhesion Molecules/chemistry
• Cell Adhesion Molecules/genetics
• Cell Adhesion Molecules/metabolism
• Conserved Sequence/genetics
• Evolution, Molecular
• Gene Duplication/genetics
• Humans
• Mice
• Multigene Family/genetics
• Nerve Tissue Proteins/chemistry
• Nerve Tissue Proteins/genetics
• Nerve Tissue Proteins/metabolism
• Neuropeptides/metabolism
• Phylogeny
• Protein Binding
• Sequence Alignment
• Sequence Analysis, Protein
• Two-Hybrid System Techniques
• beta-Galactosidase/metabolism

• Amino Acid Sequence
• Animals
• Behavior, Animal
• Cell Death
• Drosophila/chemistry
• Drosophila/enzymology
• Drosophila/genetics
• Drosophila/physiology
• Drosophila Proteins/genetics
• Drosophila Proteins/metabolism
• Humans
• Molecular Sequence Data
• Mutation
• Presynaptic Terminals/chemistry
• Presynaptic Terminals/metabolism
• Protein Kinases/chemistry
• Protein Kinases/genetics
• Protein Kinases/metabolism
• Sequence Alignment

• Animals
• Endosomes/metabolism
• Humans
• Neurites/metabolism
• Neurons/metabolism
• Protein Serine-Threonine Kinases/metabolism
• Protein Transport

• NS035546 NINDS NIH HHS
• Howard Hughes Medical Institute

• Animals
• Base Sequence
• Brain/growth & development
• Brain/physiopathology
• Central Nervous System Stimulants/pharmacology
• DNA Primers/genetics
• DNA-Binding Proteins/deficiency
• DNA-Binding Proteins/genetics
• DNA-Binding Proteins/physiology
• Disease Models, Animal
• Dizocilpine Maleate/pharmacology
• Dopamine/metabolism
• Humans
• Interneurons/metabolism
• Learning/physiology
• Male
• Memory/physiology
• Methamphetamine/pharmacology
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Motor Activity/drug effects
• Motor Activity/genetics
• Motor Activity/physiology
• Nerve Tissue Proteins/deficiency
• Nerve Tissue Proteins/genetics
• Nerve Tissue Proteins/physiology
• Phenotype
• RNA, Messenger/genetics
• RNA, Messenger/metabolism
• Schizophrenia/etiology
• Schizophrenia/genetics
• Schizophrenia/physiopathology
• Synaptic Transmission/drug effects
• gamma-Aminobutyric Acid/metabolism