TY - JOUR
T1 - Establishment of epithelial polarity - GEF who's minding the GAP?
AU - Ngok, Siu P.
AU - Lin, Wan Hsin
AU - Anastasiadis, Panos Z.
PY - 2014
Y1 - 2014
N2 - Cell polarization is a fundamental process that underlies epithelial morphogenesis, cell motility, cell division and organogenesis. Loss of polarity predisposes tissues to developmental disorders and contributes to cancer progression. The formation and establishment of epithelial cell polarity is mediated by the cooperation of polarity protein complexes, namely the Crumbs, partitioning defective (Par) and Scribble complexes, with Rho family GTPases, including RhoA, Rac1 and Cdc42. The activation of different GTPases triggers distinct downstream signaling pathways to modulate protein-protein interactions and cytoskeletal remodeling. The spatio-temporal activation and inactivation of these small GTPases is tightly controlled by a complex interconnected network of different regulatory proteins, including guanine-nucleotide-exchange factors (GEFs), GTPase-activating proteins (GAPs), and guaninenucleotide- dissociation inhibitors (GDIs). In this Commentary, we focus on current understanding on how polarity complexes interact with GEFs and GAPs to control the precise location and activation of Rho GTPases (Crumbs for RhoA, Par for Rac1, and Scribble for Cdc42) to promote apical-basal polarization in mammalian epithelial cells. The mutual exclusion of GTPase activities, especially that of RhoA and Rac1, which is well established, provides a mechanism through which polarity complexes that act through distinct Rho GTPases function as cellular rheostats to finetune specific downstream pathways to differentiate and preserve the apical and basolateral domains.
AB - Cell polarization is a fundamental process that underlies epithelial morphogenesis, cell motility, cell division and organogenesis. Loss of polarity predisposes tissues to developmental disorders and contributes to cancer progression. The formation and establishment of epithelial cell polarity is mediated by the cooperation of polarity protein complexes, namely the Crumbs, partitioning defective (Par) and Scribble complexes, with Rho family GTPases, including RhoA, Rac1 and Cdc42. The activation of different GTPases triggers distinct downstream signaling pathways to modulate protein-protein interactions and cytoskeletal remodeling. The spatio-temporal activation and inactivation of these small GTPases is tightly controlled by a complex interconnected network of different regulatory proteins, including guanine-nucleotide-exchange factors (GEFs), GTPase-activating proteins (GAPs), and guaninenucleotide- dissociation inhibitors (GDIs). In this Commentary, we focus on current understanding on how polarity complexes interact with GEFs and GAPs to control the precise location and activation of Rho GTPases (Crumbs for RhoA, Par for Rac1, and Scribble for Cdc42) to promote apical-basal polarization in mammalian epithelial cells. The mutual exclusion of GTPase activities, especially that of RhoA and Rac1, which is well established, provides a mechanism through which polarity complexes that act through distinct Rho GTPases function as cellular rheostats to finetune specific downstream pathways to differentiate and preserve the apical and basolateral domains.
KW - Cell adhesion
KW - Cell polarity
KW - Crumbs
KW - Par3
KW - Rho GTPase
KW - Scribble
UR - http://www.scopus.com/inward/record.url?scp=84905473528&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84905473528&partnerID=8YFLogxK
U2 - 10.1242/jcs.153197
DO - 10.1242/jcs.153197
M3 - Comment/debate
C2 - 24994932
AN - SCOPUS:84905473528
SN - 0021-9533
VL - 127
SP - 3205
EP - 3215
JO - Journal of cell science
JF - Journal of cell science
IS - 15
ER -