Mechanisms of isoform specific Rap2 signaling during enterocytic brush border formation.

Autor: Bruurs LJ; Molecular Cancer Research and Cancer Genomics Netherlands, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands., Bos JL; Molecular Cancer Research and Cancer Genomics Netherlands, Center for Molecular Medicine, University Medical Center Utrecht, Utrecht, The Netherlands.
Jazyk: angličtina
Zdroj: PloS one [PLoS One] 2014 Sep 09; Vol. 9 (9), pp. e106687. Date of Electronic Publication: 2014 Sep 09 (Print Publication: 2014).
DOI: 10.1371/journal.pone.0106687
Abstrakt: Brush border formation during polarity establishment of intestinal epithelial cells is uniquely governed by the Rap2A GTPase, despite expression of the other highly similar Rap2 isoforms (Rap2B and Rap2C). We investigated the mechanisms of this remarkable specificity and found that Rap2C is spatially segregated from Rap2A signaling as it is not enriched at the apical membrane after polarization. In contrast, both Rap2A and Rap2B are similarly located at Rab11 positive apical recycling endosomes and inside the brush border. However, although Rap2B localizes similarly it is not equally activated as Rap2A during brush border formation. We reveal that the C-terminal hypervariable region allows selective activation of Rap2A, yet this selectivity does not originate from the known differential lipid modifications of this region. In conclusion, we demonstrate that Rap2 specificity during brush border formation is determined by two distinct mechanisms involving segregated localization and selective activation.
Databáze: MEDLINE