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NHERF1 regulates actin cytoskeleton organization through modulation of α‐actinin‐4 stability
Author(s) -
Sun Licui,
Zheng Junfang,
Wang Qiqi,
Song Ran,
Liu Hua,
Meng Ran,
Tao Tao,
Si Yang,
Jiang Wenguo,
He Junqi
Publication year - 2016
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.15-275586
Subject(s) - microbiology and biotechnology , cytoskeleton , actin cytoskeleton , actin binding protein , actin remodeling , actin , chemistry , pdz domain , mdia1 , actinin , biology , cell , biochemistry
The actin cytoskeleton is composed of a highly dynamic network of filamentous proteins, yet the molecular mechanism that regulates its organization and remodeling remains elusive. In this study, Na + /H + exchanger regulatory factor (NHERF)‐1 loss‐of‐function and gain‐of‐function experiments reveal that polymerized actin cytoskeleton (F‐actin) in HeLa cells is disorganized by NHERF1, whereas actin protein expression levels exhibit no detectable change. To elucidate the molecular mechanism underlying actin cytoskeleton disorganization by NHERF1, a combined 2‐dimensional electrophoresis‐matrix‐assisted laser desorption/ionization‐time of flight mass spectrometry approach was used to screen for proteins regulated by NHERF1 in HeLa cells. α‐Actinin‐4, an actin cross‐linking protein, was identified. Glutathione S ‐transferase pull‐down and coimmunoprecipitation studies showed the α‐actinin‐4 carboxyl‐terminal region specifically interacted with the NHERF1 postsynaptic density 95/disc‐large/zona occludens‐1 domain. The NHERF1/α‐actinin‐4 interaction increased α‐actinin‐4 ubiquitination and decreased its expression levels, resulting in actin cytoskeleton disassembly. Our study identified α‐actinin‐4 as a novel NHERF1 interaction partner and provided new insights into the regulatory mechanism of the actin cytoskeleton by NHERF1.—Sun, L., Zheng, J., Wang, Q., Song, R., Liu, H., Meng, R., Tao T., Si, Y., Jiang, W., He, J. NHERF1 regulates actin cytoskeleton organization through modulation of α‐actinin‐4 stability. FASEB J. 30, 578‐589 (2016). www.fasebj.org