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Originally published as MBC in Press, 10.1091/mbc.E06-02-0112 on June 7, 2006

Vol. 17, Issue 8, 3651-3663, August 2006

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Calsyntenin-1 Docks Vesicular Cargo to Kinesin-1Formula Formula

Anetta Konecna*,{dagger}, Renato Frischknecht*,{dagger},{ddagger}, Jochen Kinter*,{dagger}, Alexander Ludwig*,{dagger}, Martin Steuble*,{dagger}, Virginia Meskenaite*, Martin Indermühle*, Marianne Engel*, Chuan Cen*, José-Maria Mateos§, Peter Streit§, and Peter Sonderegger*

*Department of Biochemistry and §Brain Research Institute, University of Zurich, CH-8057 Zürich, Switzerland; and {ddagger}Leibniz Institute for Neurobiology, 39 118 Magdeburg, Germany

Submitted February 7, 2006; Revised May 8, 2006; Accepted May 31, 2006
Monitoring Editor: Randy Schekman

We identified a direct interaction between the neuronal transmembrane protein calsyntenin-1 and the light chain of Kinesin-1 (KLC1). GST pulldowns demonstrated that two highly conserved segments in the cytoplasmic domain of calsyntenin-1 mediate binding to the tetratricopeptide repeats of KLC1. A complex containing calsyntenin-1 and the Kinesin-1 motor was isolated from developing mouse brain and immunoelectron microscopy located calsyntenin-1 in association with tubulovesicular organelles in axonal fiber tracts. In primary neuronal cultures, calsyntenin-1–containing organelles were aligned along microtubules and partially colocalized with Kinesin-1. Using live imaging, we showed that these organelles are transported along axons with a velocity and processivity typical for fast axonal transport. Point mutations in the two kinesin-binding segments of calsyntenin-1 significantly reduced binding to KLC1 in vitro, and vesicles bearing mutated calsyntenin-1 exhibited a markedly altered anterograde axonal transport. In summary, our results indicate that calsyntenin-1 links a certain type of vesicular and tubulovesicular organelles to the Kinesin-1 motor.


This article was published online ahead of print in MBC in Press (http://www.molbiolcell.org/cgi/doi/10.1091/mbc.E06-02-0112) on June 7, 2006.

Formula Formula The online version of this article contains supplemental material at MBC Online (http://www.molbiolcell.org).

{dagger} These authors contributed equally to this work.

Address correspondence to: Peter Sonderegger ( pson{at}bioc.unizh.ch)

Abbreviations used: KHC, kinesin heavy chain; KLC, kinesin light chain; TPR, tetratricopeptide repeat; Cst, calsyntenin; KBS, KLC1-binding segment; wt, wild-type; W1, calsyntenin-1 mutated in KBS1; W2, calsyntenin-1 mutated in KBS2; WW, calsyntenin-1 mutated in KBS1 and KBS2; DIV, day in vitro; aa, amino acid




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