Dictyostelium ACAP-A is an ArfGAP involved in cytokinesis, cell migration and actin cytoskeleton dynamics

Author:

Dias Marco,Blanc Cédric,Thazar-Poulot Nelcy,Ben Larbi Sabrina,Cosson Pierre,Letourneur François

Abstract

ACAPs and ASAPs are Arf-GTPase-activating proteins with BAR, PH, GAP and ankyrin repeat domains and are known to regulate vesicular traffic and actin cytoskeleton dynamics in mammalian cells. The amoeba Dictyostelium has only two proteins with this domain organization instead of six in human, enabling a more precise functional analysis. Genetic invalidation of acapA, resulted in multinucleated cells with cytokinesis defects. Mutant acapA− cells were hardly motile and their multicellular development was significantly delayed. In addition, formation of filopodial protrusions was deficient in these cells. Conversely, re-expression of ACAP-A-GFP resulted in numerous and long filopodia-like protrusions. Mutagenesis studies showed that ACAP-A actin remodeling function was dependent on its ability to activate its substrate, the small GTPase ArfA. Likewise, the expression of a constitutively active ArfA•GTP mutant in wild-type cells led to a significant reduction of filopodia length. Together our data support a role for ACAP-A in the control of the actin cytoskeleton organization and dynamics through an ArfA-dependent mechanism.

Publisher

The Company of Biologists

Subject

Cell Biology

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