TY - JOUR
T1 - The formin INF2 regulates basolateral-to-apical transcytosis and lumen formation in association with Cdc42 and MAL2
AU - Madrid, Ricardo
AU - Aranda, Juan F.
AU - Rodríguez-Fraticelli, Alejo E.
AU - Ventimiglia, Leandro
AU - Andrés-Delgado, Laura
AU - Shehata, Mona
AU - Fanayan, Susan
AU - Shahheydari, Hamideh
AU - Gómez, Sergio
AU - Jiménez, Alberto
AU - Martín-Belmonte, Fernando
AU - Byrne, Jennifer A.
AU - Alonso, Miguel A.
PY - 2010/5
Y1 - 2010/5
N2 - Transcytosis is a widespread pathway for apical targeting in epithelial cells. MAL2, an essential protein of the machinery for apical transcytosis, functions by shuttling in vesicular carriers between the apical zone and the cell periphery. We have identified INF2, an atypical formin with actin polymerization and depolymerization activities, which is a binding partner of MAL2. MAL2-positive vesicular carriers associate with short actin filaments during transcytosis in a process requiring INF2. INF2 binds Cdc42 in a GTP-loaded-dependent manner. Cdc42 and INF2 regulate MAL2 dynamics and are necessary for apical transcytosis and the formation of lateral lumens in hepatoma HepG2 cells. INF2 and MAL2 are also essential for the formation of the central lumen in organotypic cultures of epithelial MDCK cells. Our results reveal a functional mechanism whereby Cdc42, INF2, and MAL2 are sequentially ordered in a pathway dedicated to the regulation of transcytosis and lumen formation.
AB - Transcytosis is a widespread pathway for apical targeting in epithelial cells. MAL2, an essential protein of the machinery for apical transcytosis, functions by shuttling in vesicular carriers between the apical zone and the cell periphery. We have identified INF2, an atypical formin with actin polymerization and depolymerization activities, which is a binding partner of MAL2. MAL2-positive vesicular carriers associate with short actin filaments during transcytosis in a process requiring INF2. INF2 binds Cdc42 in a GTP-loaded-dependent manner. Cdc42 and INF2 regulate MAL2 dynamics and are necessary for apical transcytosis and the formation of lateral lumens in hepatoma HepG2 cells. INF2 and MAL2 are also essential for the formation of the central lumen in organotypic cultures of epithelial MDCK cells. Our results reveal a functional mechanism whereby Cdc42, INF2, and MAL2 are sequentially ordered in a pathway dedicated to the regulation of transcytosis and lumen formation.
UR - http://www.scopus.com/inward/record.url?scp=77952903622&partnerID=8YFLogxK
U2 - 10.1016/j.devcel.2010.04.001
DO - 10.1016/j.devcel.2010.04.001
M3 - Article
C2 - 20493814
AN - SCOPUS:77952903622
SN - 1534-5807
VL - 18
SP - 814
EP - 827
JO - Developmental Cell
JF - Developmental Cell
IS - 5
ER -