A unique residue in rab3c determines the interaction with novel binding protein Zwint-1

van Vlijmen, Thijs; Vleugel, Mathijs; Evers, Melvin; Mohammed, Shabaz; Wulf, Phebe S.; Heck, Albert J.R.; Hoogenraad, Casper C.; van der Sluijs, Peter

doi:10.1016/j.febslet.2008.07.012

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Volume 582, Issue 19 , Pages 2838-2842, 20 August 2008

A unique residue in rab3c determines the interaction with novel binding protein Zwint-1

Edited by Maurice Montal

Thijs van Vlijmen
- Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
- Contributed equally.
Mathijs Vleugel
- Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
- Contributed equally.
Melvin Evers
- Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
Shabaz Mohammed
- Department of Bio-molecular Mass Spectrometry, Utrecht University, 3584 CA Utrecht, The Netherlands
Phebe S. Wulf
- Department of Neuroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands
Albert J.R. Heck
- Department of Bio-molecular Mass Spectrometry, Utrecht University, 3584 CA Utrecht, The Netherlands
Casper C. Hoogenraad
- Department of Neuroscience, Erasmus Medical Center, 3000 CA Rotterdam, The Netherlands
Peter van der Sluijs
- Department of Cell Biology, University Medical Center Utrecht, 3584 CX Utrecht, The Netherlands
- Corresponding author. Address: Department of Cell Biology, University Medical Center, P.O. Box 85500, 3508 GA Utrecht, The Netherlands. Fax: +31 30 2541797.

Received 20 March 2008; received in revised form 2 July 2008; accepted 3 July 2008. published online 14 July 2008.

Abstract

Exocytic events are tightly regulated cellular processes in which rab GTPases and their interacting proteins perform an important function. We set out to identify new binding partners of rab3, which mediates regulated secretion events in specialized cells. We discovered Zwint-1 as a rab3 specific binding protein that bound preferentially to rab3c. The interaction depends on a critical residue in rab3c that determines the binding efficiency of Zwint-1, which is immaterial for interaction with rabphilin3a. Rab3c and Zwint-1 are expressed highly in brain and colocalized extensively in primary hippocampal neurons. We also found that SNAP25 bound to the same region in Zwint-1 as rab3c, suggesting a new role for the kinetochore protein Zwint-1 in presynaptic events that are regulated by rab3 and SNAP25.

Keywords: Rab3, Zwint-1, Rabphilin3a, SNAP25