The polarity protein Inturned links NPHP4 to Daam1 to control the subapical actin network in multiciliated cells

被引：39

作者：

Yasunaga, Takayuki ^{[1
]}

Hoff, Sylvia ^{[1
]}

Schell, Christoph ^{[1
]}

Helmstaedter, Martin ^{[1
]}

Kretz, Oliver ^{[1
,2
]}

Kuechlin, Sebastian ^{[1
]}

Yakulov, Toma A. ^{[1
]}

Engel, Christina ^{[1
]}

Mueller, Barbara ^{[1
]}

Bensch, Robert ^{[3
,4
]}

Ronneberger, Olaf ^{[3
,4
]}

Huber, Tobias B. ^{[1
,4
]}

Lienkamp, Soeren S. ^{[1
,4
]}

Walz, Gerd ^{[1
,4
]}

机构：

[1] Univ Freiburg, Med Ctr, Dept Med, Div Renal, Hugstetter Str 55, D-79106 Freiburg, Germany

[2] Univ Freiburg, Neuroanat, D-79104 Freiburg, Germany

[3] Univ Freiburg, Dept Comp Sci, D-79110 Freiburg, Germany

[4] Ctr Biol Signaling Studies, D-79104 Freiburg, Germany

来源：

JOURNAL OF CELL BIOLOGY | 2015年 / 211卷 / 05期

关键词：

TRANSITION ZONE; SITUS-INVERSUS; DISEASE GENES; BASAL BODIES; CILIOGENESIS; ROLES; CILIA; FUZZY; NEPHROCYSTIN-4; LOCALIZES;

D O I：

10.1083/jcb.201502043

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

Motile cilia polarization requires intracellular anchorage to the cytoskeleton; however, the molecular machinery that supports this process remains elusive. We report that Inturned plays a central role in coordinating the interaction between cilia-associated proteins and actin-nucleation factors. We observed that knockdown of nphp4 in multiciliated cells of the Xenopus laevis epidermis compromised ciliogenesis and directional fluid flow. Depletion of nphp4 disrupted the subapical actin layer. Comparison to the structural defects caused by inturned depletion revealed striking similarities. Furthermore, coimmunoprecipitation assays demonstrated that the two proteins interact with each other and that Inturned mediates the formation of ternary protein complexes between NPHP4 and DAAM1. Knockdown of daam1, but not formin-2, resulted in similar disruption of the subapical actin web, whereas nphp4 depletion prevented the association of Inturned with the basal bodies. Thus, Inturned appears to function as an adaptor protein that couples cilia-associated molecules to actin-modifying proteins to rearrange the local actin cytoskeleton.

引用

页码：963 / 973

页数：11