JCB logo
Avanti Polar Lipids, Inc.
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
This Article
Right arrow Full Text
Right arrow Full Text (PDF, 1496K)
Right arrow PPT slides of all figures
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JCB
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Laux, T.
Right arrow Articles by Caroni, P.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Laux, T.
Right arrow Articles by Caroni, P.
Related Collections
Right arrowRelated Article
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Facebook   Add to Reddit   Add to Technorati   Add to Twitter  
What's this?

© The Rockefeller University Press, 0021-9525/2000//1455 $5.00
The Journal of Cell Biology, Volume 149, Number 7, , 2000 1455-1472

Original Article

Gap43, Marcks, and Cap23 Modulate Pi(4,5)p2 at Plasmalemmal Rafts, and Regulate Cell Cortex Actin Dynamics through a Common Mechanism



Thorsten Lauxa, Kiyoko Fukamib, Marcus Thelenc, Tamara Goluba, Dunja Freya, and Pico Caronia

a Friedrich Miescher Institute, CH-4058 Basel, Switzerland
b Department of Biochemistry, Institute of Medical Sciences, Tokyo, Japan
c Theodor Kocher Institut, Bern, Switzerland
Friedrich Miescher Institute, Maulbeerstrasse 66, CH-4058 Basel, Switzerland.41-61-697-397641-61-697-3727

caroni{at}fmi.ch

The dynamic properties of the cell cortex and its actin cytoskeleton determine important aspects of cell behavior and are a major target of cell regulation. GAP43, myristoylated alanine-rich C kinase substrate (MARCKS), and CAP23 (GMC) are locally abundant, plasmalemma-associated PKC substrates that affect actin cytoskeleton. Their expression correlates with morphogenic processes and cell motility, but their role in cortex regulation has been difficult to define mechanistically. We now show that the three proteins accumulate at rafts, where they codistribute with PI(4,5)P2, and promote its retention and clustering. Binding and modulation of PI(4,5)P2 depended on the basic effector domain (ED) of these proteins, and constructs lacking the ED functioned as dominant inhibitors of plasmalemmal PI(4,5)P2 modulation. In the neuronlike cell line, PC12, NGF- and substrate-induced peripheral actin structures, and neurite outgrowth were greatly augmented by any of the three proteins, and suppressed by {Delta}ED mutants. Agents that globally mask PI(4,5)P2 mimicked the effects of GMC on peripheral actin recruitment and cell spreading, but interfered with polarization and process formation. Dominant negative GAP43({Delta}ED) also interfered with peripheral nerve regeneration, stimulus-induced nerve sprouting and control of anatomical plasticity at the neuromuscular junction of transgenic mice. These results suggest that GMC are functionally and mechanistically related PI(4,5)P2 modulating proteins, upstream of actin and cell cortex dynamics regulation.

Key Words: neurite outgrowth • cell spreading • anatomical plasticity • actin recruitment • lipid microdomain

© 2000 The Rockefeller University Press

Abbreviations used in this paper: CaM, calmodulin; GMC, GAP23, MARCKS, and CAP23; MARCKS, myristoylated alanine-rich C kinase substrate; ED, effector domain; PKC, protein kinase C; PLC, phospholipase C.


Add to CiteULike CiteULike   Add to Complore Complore   Add to Connotea Connotea   Add to Del.icio.us Del.icio.us   Add to Digg Digg   Add to Facebook Facebook   Add to Reddit Reddit   Add to Technorati Technorati   Add to Twitter Twitter    What's this?

Related Article


J. Cell Biol. 2000 149: 1-2. [Full Text] [PDF]





  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents