Current Biology
Volume 7, Issue 8, 1 August 1997, Pages 611-614
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Brief Communication
MARCKS regulates membrane ruffling and cell spreading

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Abstract

The dynamic rearrangement of the actin cytoskeleton is fundamental to most biological processes including embryogenesis, morphogenesis, cell movement, wound healing and metastasis [1]. Membrane ruffling and reversible cell–substratum interactions underlie actin-driven cell movement. Protein kinase C (PKC) stimulates membrane ruffling and adhesion [2], but the mechanism by which this occurs is unknown. Myristoylated alanine-rich C kinase substrate (MARCKS) is a PKC substrate that cycles on and off membranes by a mechanism termed the myristoyl–electrostatic switch [3], [4], [5], [6]. While at the membrane, MARCKS binds to and sequesters acidic phospholipids including phosphatidyl-inositol-4,5-bisphosphate (PIP2) [7]. MARCKS also binds and cross-links filamentous actin, an activity which is regulated by PKC-dependent phosphorylation and calcium–calmodulin [8]. In this report, we demonstrate that expression, in fibroblasts, of MARCKS containing a mutation which abrogates the myristoyl–electrostatic switch prevents cell spreading. The MARCKS mutant arrests the cell during an early stage of spreading, characterized by profuse membrane blebbing, and prevents the formation of membrane ruffles and lamellae usually found at the leading edge of spreading cells. This defect in the regulation of the actin cytoskeleton is accompanied by a decrease in cell–substratum adhesion. Our results provide direct evidence that MARCKS and PKC regulate actin-dependent membrane ruffling and cell adhesion, perhaps via a PIP2-dependent mechanism.

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MM Myat, S Anderson and A Aderem, University of Washington, Department of Immunology, Box 357650, Seattle, Washington 98195-7650, USA.

LAH Allen, University of lowa, Department of Internal Medicine, Division of Infectious Diseases, 200 Hawkins Drive, lowa City, lowa 52242, USA.

E-mail address for A Aderem (corresponding author): [email protected].