small GTPases of the Ras superfamily in epithelial biogenesis

The small GTPases of the Ras superfamily play critical roles in epithelial biogenesis. Many key morphogenetic functions occur when small GTPases act at epithelial junctions, where they mediate an increasingly complex interplay between cell-cell adhesion molecules and fundamental cellular processes, such as cytoskeletal activity, polarity and trafficking.

Important recent advances in this field include the role of additional members of the Ras superfamily in cell-cell contact stability and the capacity for polarity determinants to regulate small GTPase signalling.

The small GTPases may participate in the cross-talk between different adhesive receptors: in tissues classical cadherins can selectively regulate other junctions through cell signalling rather than through a global influence on cell-cell cohesion.

Members

SARAs are the Sar1-ADP-ribosylation factor family of small GTPases, which govern the intracellular trafficking of proteins in coat protein (COP)-coated vesicles.

Pathology

 SARA2 mutations in

• chylomicron retention disease (MIM.246700)
• Anderson disease (MIM.607689)
• chylomicron retention disease with Marinesco-Sjogren syndrome (MIM.607692)

References

 Braga VM, Yap AS. The challenges of abundance: epithelial junctions and small GTPase signalling. Curr Opin Cell Biol. 2005 Oct;17(5):466-74. PMID: #16112561#