English
 
User Manual Privacy Policy Disclaimer Contact us
  Advanced SearchBrowse

Item

ITEM ACTIONSEXPORT
  Localization versus function of Rab3 proteins - Evidence for a common regulatory role in controlling fusion

Schlueter, O. M., Khvotchev, M., Jahn, R., & Suedhof, T. C. (2002). Localization versus function of Rab3 proteins - Evidence for a common regulatory role in controlling fusion. Journal of Biological Chemistry, 277(43), 40919-40929. Retrieved from http://www.jbc.org/content/277/43/40919.full.pdf+html.

Item is

Basic

show hide
Item Permalink: http://hdl.handle.net/11858/00-001M-0000-0012-F2B7-B Version Permalink: http://hdl.handle.net/11858/00-001M-0000-0028-E28B-F
Genre: Journal Article

Files

show Files
hide Files
:
599464.pdf (Publisher version), 935KB
Name:
599464.pdf
Description:
-
Visibility:
Public
MIME-Type / Checksum:
application/pdf / [MD5]
Technical Metadata:
Copyright Date:
-
Copyright Info:
-
License:
-

Locators

show

Creators

show
hide
 Creators:
Schlueter, O. M.1, Author              
Khvotchev, M., Author
Jahn, R.1, Author              
Suedhof, T. C., Author
Affiliations:
1Department of Neurobiology, MPI for biophysical chemistry, Max Planck Society, ou_578595              

Content

show
hide
Free keywords: -
 Abstract: Rab3A, Rab3B, Rab3C, and Rab3D constitute a family of GTP- binding proteins that are implicated in regulated exocytosis. Various localizations and distinct functions have been proposed for different and occasionally even for the same Rab3 protein. This is exemplified by studies demonstrating that deletion of Rab3A in knock-out mice results in dysregulation of the final stages of exocytosis, whereas overexpression of Rab3A in neuroendocrine cells causes nearly complete inhibition of Ca2+- triggered exocytosis. We have now examined the properties of all Rab3 proteins in the same assays, with the long-term goal of identifying a common conceptual framework for their functions. Using quantitative immunoblotting, we found that all four Rab3 proteins were expressed in brain and endocrine tissues, although at widely different levels. Rab3A, Rab3B, and Rab3C co-localized to synaptic and secretory vesicles consistent with potential redundancy, whereas Rab3D was expressed at high levels only in the endocrine pituitary (where it was more abundant than Rab3A, Rab3B, and Rab3C combined), in exocrine glands, and in adipose tissue. In transfected PC12 cells, all four Rab3 proteins strongly inhibited Ca2+-triggered exocytosis. Except for a mutation that fixes Rab3 into a permanently GDP-bound state, all Rab3 mutations tested had no effect on this inhibition, including a mutation in the calmodulin-binding site that was described as inactivating (Coppola, T., Perret-Menoud, V., Luthi, S., Farnsworth, C. C., Glomset, J. A., and Regazzi, R. (1999) EMBO J. 18, 5885- 5891).:Unexpectedly, overexpression of wild type Rab3A and permanently GTP-bound mutant Rab3A in PC12 cells caused a loss of secretory vesicles and an increase in constitutive, Ca2+- independent exocytosis that correlated with the inhibition of regulated Ca2+-triggered exocytosis. Our data indicate that overexpression of Rab3 in PC12 cells impairs the normal control of the final step in exocytosis, thereby converting the regulated secretory pathway into a constitutive pathway. These results offer an hypothesis that reconciles Rab3 transfection and knockout studies by suggesting that Rab3 functions as a gatekeeper of a late stage in exocytosis.

Details

show
hide
Language(s): eng - English
 Dates: 2002-10-25
 Publication Status: Published in print
 Pages: -
 Publishing info: -
 Table of Contents: -
 Rev. Method: Peer
 Degree: -

Event

show

Legal Case

show

Project information

show

Source 1

show
hide
Title: Journal of Biological Chemistry
Source Genre: Journal
 Creator(s):
Affiliations:
Publ. Info: -
Pages: - Volume / Issue: 277 (43) Sequence Number: - Start / End Page: 40919 - 40929 Identifier: -