Universität zu Köln

Yao, Gang, Su, Xuefeng, Roberts, Kristina, Li, Xiaogang, Takakura, Ayumi, Plomann, Markus and Zhou, Jing (2014). Polycystin-1 regulates actin cytoskeleton organization and directional cell migration through a novel PC1-Pacsin 2-N-Wasp complex. Hum. Mol. Genet., 23 (10). S. 2769 - 2780. OXFORD: OXFORD UNIV PRESS. ISSN 1460-2083

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Abstract

How epithelial cells form a tubule with defined length and lumen diameter remains a fundamental question in cell and developmental biology. Loss of control of tubule lumen size in multiple organs including the kidney, liver and pancreas features polycystic kidney disease (PKD). To gain insights into autosomal dominant polycystic kidney disease, we performed yeast two-hybrid screens using the C-terminus of polycystin-1 (PC1) as bait. Here, we report that PC1 interacts with Pacsin 2, a cytoplasmic phosphoprotein that has been implicated in cytoskeletal organization, vesicle trafficking and more recently in cell intercalation during gastrulation. PC1 binds to a 107-residue fragment containing the 3 helix of the F-BAR domain of Pacsin 2 via a coiled-coil domain in its C-tail. PC1 and Pacsin 2 co-localize on the lamellipodia of migrating kidney epithelial cells. PC1 and Pacsin 2-deficient kidney epithelial cells migrate at a slower speed with reduced directional persistency. We further demonstrate that PC1, Pacsin 2 and N-Wasp are in the same protein complex, and both PC1 and Pacsin 2 are required for N-Wasp/Arp2/3-dependent actin remodeling. We propose that PC1 modulates actin cytoskeleton rearrangements and directional cell migration through the Pacsin 2/N-Wasp/Arp2/3 complex, which consequently contributes to the establishment and maintenance of the sophisticated tubular architecture. Disruption of this complex contributes to cyst formation in PKD.

Item Type:	Journal Article
Creators:	Creators Email ORCID ORCID Put Code Yao, Gang UNSPECIFIED UNSPECIFIED UNSPECIFIED Su, Xuefeng UNSPECIFIED UNSPECIFIED UNSPECIFIED Roberts, Kristina UNSPECIFIED UNSPECIFIED UNSPECIFIED Li, Xiaogang UNSPECIFIED UNSPECIFIED UNSPECIFIED Takakura, Ayumi UNSPECIFIED UNSPECIFIED UNSPECIFIED Plomann, Markus UNSPECIFIED UNSPECIFIED UNSPECIFIED Zhou, Jing UNSPECIFIED UNSPECIFIED UNSPECIFIED
URN:	urn:nbn:de:hbz:38-438302
DOI:	10.1093/hmg/ddt672
Journal or Publication Title:	Hum. Mol. Genet.
Volume:	23
Number:	10
Page Range:	S. 2769 - 2780
Date:	2014
Publisher:	OXFORD UNIV PRESS
Place of Publication:	OXFORD
ISSN:	1460-2083
Language:	English
Faculty:	Unspecified
Divisions:	Unspecified
Subjects:	no entry
Uncontrolled Keywords:	Keywords Language EXTRACELLULAR-MATRIX PROTEINS; KIDNEY-DISEASE; PACSIN 2; N-WASP; PKD1; IDENTIFICATION; PHOSPHORYLATION; TUBULOGENESIS; LOCALIZATION; MOTILITY Multiple languages Biochemistry & Molecular Biology; Genetics & Heredity Multiple languages
URI:	http://kups.ub.uni-koeln.de/id/eprint/43830