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EGFR controls IQGAP basolateral membrane localization and mitotic spindle orientation during epithelial morphogenesis
Author(s) -
BañónRodríguez Inmaculada,
GálvezSantisteban Manuel,
Vergarajauregui Silvia,
Bosch Minerva,
BorregueroPascual Arantxa,
MartínBelmonte Fernando
Publication year - 2014
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/embj.201385946
Subject(s) - iqgap1 , microbiology and biotechnology , biology , epithelial polarity , mitosis , cell polarity , morphogenesis , spindle apparatus , cell cortex , cell division , cell , cytoskeleton , scaffold protein , signal transduction , genetics , gene
Establishing the correct orientation of the mitotic spindle is an essential step in epithelial cell division in order to ensure that epithelial tubules form correctly during organ development and regeneration. While recent findings have identified some of the molecular mechanisms that underlie spindle orientation, many aspects of this process remain poorly understood. Here, we have used the 3 D ‐ MDCK model system to demonstrate a key role for a newly identified protein complex formed by IQGAP 1 and the epithelial growth factor receptor ( EGFR ) in controlling the orientation of the mitotic spindle. IQGAP 1 is a scaffolding protein that regulates many cellular pathways, from cell‐cell adhesion to microtubule organization, and its localization in the basolateral membrane ensures correct spindle orientation. Through its IQ motifs, IQGAP 1 binds to EGFR , which is responsible for maintaining IQGAP 1 in the basolateral membrane domain. Silencing IQGAP 1, or disrupting the basolateral localization of either IQGAP 1 or EGFR , results in a non‐polarized distribution of NuMA , mitotic spindle misorientation and defects in single lumen formation.