NDLI: Laminin regulates mouse embryonic stem cell migration: involvement of Epac1/Rap1 and Rac1/cdc42.

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Laminin regulates mouse embryonic stem cell migration: involvement of Epac1/Rap1 and Rac1/cdc42.

Content Provider	Semantic Scholar
Copyright Year	2010
Abstract	Laminin is the first extracellular matrix (ECM) component to be expressed in the developing mammalian embryo. However, the roles of laminin or the related signal pathways are not well known in mouse embryonic stem cells (mESCs). Presently, we examined the effect of laminin on mESC migration. Laminin (10 microg/ml) decreased cell aggregation, whereas migration was increased. Laminin bound alpha6beta1 integrin and laminin receptor 1 (LR1), decreasing their mRNA levels. Laminin increased focal adhesion kinase (FAK) and paxillin phosphorylation, cAMP intracellular concentration, and the protein levels of exchange factor directly activated by cAMP (Epac1) and Rap1. These increases were completely blocked by alpha6beta1 integrin and LR1 neutralizing antibody, indicating that laminin-bound LR1 assists laminin-induced alpha6beta1 integrin activity and initiates signal. As a downstream signal molecule, laminin activated small G protein such as Rac1/cdc42 and its effector protein p21-activated kinase (PAK). Subsequently, laminin stimulated E-cadherin complex disruption. Inhibition of each pathway such as those for alpha6beta1 integrin and LR1, FAK, Rap1, and PAK1 blocked laminin-induced migration. We conclude that laminin binds both alpha6beta1 integrin and LR1 and induces signaling FAK/paxillin and cAMP/Epac1/Rap1. These signaling merge at Rac1/cdc42 subsequently activate PAK1. Activated PAK1 enhances E-cadherin complex disruption and finally increases mESCs migration.
Starting Page	50
Ending Page	52
Page Count	3
File Format	PDF HTM / HTML
DOI	10.1152/ajpcell.00496.2009
PubMed reference number	20089929
Journal	Medline
Volume Number	298
Issue Number	5
Alternate Webpage(s)	http://ajpcell.physiology.org/content/ajpcell/298/5/C1159.full.pdf
Alternate Webpage(s)	https://doi.org/10.1152/ajpcell.00496.2009
Journal	American journal of physiology. Cell physiology
Language	English
Access Restriction	Open
Content Type	Text
Resource Type	Article

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