Universität zu Köln

Ramalingam, Nagendran, Zhao, Hongxia ORCID: 0000-0002-1606-5621, Breitsprecher, Dennis, Lappalainen, Pekka ORCID: 0000-0001-6227-0354, Faix, Jan and Schleicher, Michael (2010). Phospholipids regulate localization and activity of mDia1 formin. Eur. J. Cell Biol., 89 (10). S. 723 - 733. JENA: ELSEVIER GMBH, URBAN & FISCHER VERLAG. ISSN 1618-1298

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Abstract

Diaphanous-related formins (DRFs) are large multi-domain proteins that nucleate and assemble linear actin filaments. Binding of active Rho family proteins to the GTPase-binding domain (GBD) triggers localization at the membrane and the activation of most formins if not all. In recent years GTPase regulation of formins has been extensively studied, but other molecular mechanisms that determine subcellular distribution or regulate formin activity have remained poorly understood. Here, we provide evidence that the activity and localization of mouse formin mDia1 can be regulated through interactions with phospholipids. The phospholipid-binding sites of mDia1 are clusters of positively charged residues in the N-terminal basic domain (BD) and at the C-terminal region. Upon binding to the lipid bilayer the N-terminal region of mDia1 induces strong clustering of phosphatidylinositol-4,5-bisphosphate (PIP2) and subsequently inserts into the membrane bilayer thus anchoring mDia1 to the reconstituted plasma membrane. In addition, an interaction of phospholipids with the C-terminal region of mDia1 causes a drastic reduction of its actin filament assembly activity. Our data suggest that the N-terminal phospholipid-binding sites help to anchor formins at the plasma membrane, and the interaction with phospholipids in the C-terminus functions as a switch for transient inactivation. (C) 2010 Elsevier GmbH. All rights reserved.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Ramalingam, Nagendran UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhao, Hongxia UNSPECIFIED orcid.org/0000-0002-1606-5621 UNSPECIFIED Breitsprecher, Dennis UNSPECIFIED UNSPECIFIED UNSPECIFIED Lappalainen, Pekka UNSPECIFIED orcid.org/0000-0001-6227-0354 UNSPECIFIED Faix, Jan UNSPECIFIED UNSPECIFIED UNSPECIFIED Schleicher, Michael UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-495414
DOI:	10.1016/j.ejcb.2010.06.001
Journal or Publication Title:	Eur. J. Cell Biol.
Volume:	89
Number:	10
Page Range:	S. 723 - 733
Date:	2010
Publisher:	ELSEVIER GMBH, URBAN & FISCHER VERLAG
Place of Publication:	JENA
ISSN:	1618-1298
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language DIAPHANOUS-RELATED FORMINS; ACTIN-FILAMENT ELONGATION; ALDRICH-SYNDROME PROTEIN; AUTOREGULATORY DOMAIN; PHOSPHATIDYLINOSITOL 4,5-BISPHOSPHATE; BINDING DOMAINS; ARP2/3 COMPLEX; BARBED ENDS; ACTIVATION; NUCLEATION Multiple languages Cell Biology Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/49541