Synaptic Scaffolding Protein SYD-2 Clusters and Activates Kinesin-3 UNC-104 in C. Elegans

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2009 Nov 3

PMID 19880746

Citations 48

Authors

Oliver I Wagner

Alessandro Esposito

Barbara Kohler

Chih-Wei Chen

Che-Piao Shen

Gong-Her Wu

Eugenia Butkevich

Sailaja Mandalapu

Dirk Wenzel

Fred S Wouters

Dieter R Klopfenstein

Affiliations

Soon will be listed here.

Abstract

Kinesin-3 motor UNC-104/KIF1A is essential for transporting synaptic precursors to synapses. Although the mechanism of cargo binding is well understood, little is known how motor activity is regulated. We mapped functional interaction domains between SYD-2 and UNC-104 by using yeast 2-hybrid and pull-down assays and by using FRET/fluorescence lifetime imaging microscopy to image the binding of SYD-2 to UNC-104 in living Caenorhabditis elegans. We found that UNC-104 forms SYD-2-dependent axonal clusters (appearing during the transition from L2 to L3 larval stages), which behave in FRAP experiments as dynamic aggregates. High-resolution microscopy reveals that these clusters contain UNC-104 and synaptic precursors (synaptobrevin-1). Analysis of motor motility indicates bi-directional movement of UNC-104, whereas in syd-2 mutants, loss of SYD-2 binding reduces net anterograde movement and velocity (similar after deleting UNC-104's liprin-binding domain), switching to retrograde transport characteristics when no role of SYD-2 on dynein and conventional kinesin UNC-116 motility was found. These data present a kinesin scaffolding protein that controls both motor clustering along axons and motor motility, resulting in reduced cargo transport efficiency upon loss of interaction.

Citing Articles

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