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The Vesicle Protein SAM-4 Regulates the Processivity of Synaptic Vesicle Transport

Overview
Journal PLoS Genet
Specialty Genetics
Date 2014 Oct 21
PMID 25329901
Citations 30
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Abstract

Axonal transport of synaptic vesicles (SVs) is a KIF1A/UNC-104 mediated process critical for synapse development and maintenance yet little is known of how SV transport is regulated. Using C. elegans as an in vivo model, we identified SAM-4 as a novel conserved vesicular component regulating SV transport. Processivity, but not velocity, of SV transport was reduced in sam-4 mutants. sam-4 displayed strong genetic interactions with mutations in the cargo binding but not the motor domain of unc-104. Gain-of-function mutations in the unc-104 motor domain, identified in this study, suppress the sam-4 defects by increasing processivity of the SV transport. Genetic analyses suggest that SAM-4, SYD-2/liprin-α and the KIF1A/UNC-104 motor function in the same pathway to regulate SV transport. Our data support a model in which the SV protein SAM-4 regulates the processivity of SV transport.

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References
1.
Wyszynski M, Kim E, Dunah A, Passafaro M, Valtschanoff J, Serra-Pages C . Interaction between GRIP and liprin-alpha/SYD2 is required for AMPA receptor targeting. Neuron. 2002; 34(1):39-52. DOI: 10.1016/s0896-6273(02)00640-2. View

2.
Esposito G, Ana Clara F, Verstreken P . Synaptic vesicle trafficking and Parkinson's disease. Dev Neurobiol. 2011; 72(1):134-44. DOI: 10.1002/dneu.20916. View

3.
Wagner O, Esposito A, Kohler B, Chen C, Shen C, Wu G . Synaptic scaffolding protein SYD-2 clusters and activates kinesin-3 UNC-104 in C. elegans. Proc Natl Acad Sci U S A. 2009; 106(46):19605-10. PMC: 2780759. DOI: 10.1073/pnas.0902949106. View

4.
Hammond J, Cai D, Blasius T, Li Z, Jiang Y, Jih G . Mammalian Kinesin-3 motors are dimeric in vivo and move by processive motility upon release of autoinhibition. PLoS Biol. 2009; 7(3):e72. PMC: 2661964. DOI: 10.1371/journal.pbio.1000072. View

5.
Sonnichsen B, Koski L, Walsh A, Marschall P, Neumann B, Brehm M . Full-genome RNAi profiling of early embryogenesis in Caenorhabditis elegans. Nature. 2005; 434(7032):462-9. DOI: 10.1038/nature03353. View