IRTKS (BAIAP2L1) Elongates Epithelial Microvilli Using EPS8-Dependent and Independent Mechanisms.
IRTKS (BAIAP2L1) Elongates Epithelial Microvilli Using EPS8-Dependent and Independent Mechanisms.
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DOI：
10.1016/j.cub.2018.07.022
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发表时间：
2018-09-24
期刊：
影响因子：
--
通讯作者：
Tyska MJ
中科院分区：
文献类型：
--
作者：
Postema MM;Grega-Larson NE;Neininger AC;Tyska MJ
运输上皮细胞，如那些内衬肠道，建立大阵列的肌动蛋白支持的突起称为微绒毛，从顶端表面延伸到管腔空间，以增加功能表面积。虽然维持生理稳态的关键，控制微绒毛的形成机制仍然知之甚少。在这里，我们报告说，I-BAR域含有蛋白质胰岛素受体酪氨酸激酶底物（IRTKS，也称为BAIAP 2L 1）促进上皮微绒毛的生长。分化上皮细胞的超分辨率显微镜和实时成像显示，IRTKS通过需要其N-末端I-BAR结构域的机制定位于活跃生长的微绒毛的远端。在微绒毛尖端，IRTKS通过涉及其C-末端肌动蛋白结合WH 2结构域的机制促进伸长。IRTKS还可以使用其SH 3结构域将捆绑蛋白EPS 8募集到微绒毛尖端来驱动微绒毛伸长。这些结果提供了新的见解的机制，控制微绒毛生长在运输上皮细胞的分化过程中，并帮助解释为什么IRTKS是由肠道病原体，破坏微绒毛结构的肠上皮感染过程中的目标。Postema等人表明IRTKS（BAIAP 2L 1）通过其N-末端I-BAR结构域定位于活跃生长的上皮微绒毛的远端。在这些位点，IRTKS直接使用其C-末端肌动蛋白结合WH 2结构域驱动微绒毛伸长，并间接使用其SH 3结构域募集肌动蛋白调节蛋白EPS 8。
Transporting epithelial cells like those that line the gut, build large arrays of actin-supported protrusions called microvilli, which extend from the apical surface into luminal spaces to increase functional surface area. Although critical for maintaining physiological homeostasis, mechanisms controlling the formation of microvilli remain poorly understood. Here we report that the I-BAR domain containing protein insulin receptor tyrosine kinase substrate (IRTKS, also known as BAIAP2L1) promotes the growth of epithelial microvilli. Super-resolution microscopy and live imaging of differentiating epithelial cells revealed that IRTKS localizes to the distal tips of actively growing microvilli via a mechanism that requires its N-terminal I-BAR domain. At microvillar tips, IRTKS promotes elongation through a mechanism involving its C-terminal actin binding WH2 domain. IRTKS can also drive microvillar elongation using its SH3 domain to recruit the bundling protein EPS8 to microvillar tips. These results provide new insight on mechanisms that control microvillar growth during the differentiation of transporting epithelial cells, and help explain why IRTKS is targeted by enteric pathogens that disrupt microvillar structure during infection of the intestinal epithelium. Postema et al. show that IRTKS (BAIAP2L1) localizes to the distal tips of actively growing epithelial microvilli through its N-terminal I-BAR domain. At these sites, IRTKS drives microvillar elongation directly using its C-terminal actin binding WH2 domain, and indirectly using its SH3 domain to recruit the actin regulatory protein EPS8.
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影响因子：
2.9
作者：
Grega-Larson, Nathan E.;Crawley, Scott W.;Tyska, Matthew J.
通讯作者：
Tyska, Matthew J.
影响因子：
9.8
作者：
Hertzog M;Milanesi F;Hazelwood L;Disanza A;Liu H;Perlade E;Malabarba MG;Pasqualato S;Maiolica A;Confalonieri S;Le Clainche C;Offenhauser N;Block J;Rottner K;Di Fiore PP;Carlier MF;Volkmann N;Hanein D;Scita G
通讯作者：
Scita G
影响因子：
3.6
作者：
Crepin VF;Girard F;Schüller S;Phillips AD;Mousnier A;Frankel G
通讯作者：
Frankel G
影响因子：
5.7
作者：
de Groot, Jens C.;Schlueter, Kai;Carius, Yvonne;Quedenau, Claudia;Vingadassalom, Didier;Faix, Jan;Weiss, Stefanie M.;Reichelt, Joachim;Standfuss-Gabisch, Christine;Lesser, Cammie F.;Leong, John M.;Heinz, Dirk W.;Buessow, Konrad;Stradal, Theresia E. B.
通讯作者：
Stradal, Theresia E. B.
影响因子：
7.8
作者：
FRANCK, Z;FOOTER, M;BRETSCHER, A
通讯作者：
BRETSCHER, A