Title | Polarized deposition of basement membrane proteins depends on Phosphatidylinositol synthase and the levels of Phosphatidylinositol 4,5-bisphosphate. |
Publication Type | Journal Article |
Year of Publication | 2014 |
Authors | Devergne, O, Tsung, K, Barcelo, G, Schüpbach, T |
Journal | Proc Natl Acad Sci U S A |
Volume | 111 |
Issue | 21 |
Pagination | 7689-94 |
Date Published | 2014 May 27 |
ISSN | 1091-6490 |
Keywords | Animals, Basement Membrane, CDP-Diacylglycerol-Inositol 3-Phosphatidyltransferase, Cell Polarity, Cell Transformation, Neoplastic, Drosophila, Epithelial Cells, Female, Fluorescent Antibody Technique, Ovary, Phosphatidylinositol 4,5-Diphosphate |
Abstract | <p>The basement membrane (BM), a specialized sheet of the extracellular matrix contacting the basal side of epithelial tissues, plays an important role in the control of the polarized structure of epithelial cells. However, little is known about how BM proteins themselves achieve a polarized distribution. Here, we identify phosphatidylinositol 4,5-bisphosphate (PIP2) as a critical regulator of the polarized secretion of BM proteins. A decrease of PIP2 levels, in particular through mutations in Phosphatidylinositol synthase (Pis) and other members of the phosphoinositide pathway, leads to the aberrant accumulation of BM components at the apical side of the cell without primarily affecting the distribution of apical and basolateral polarity proteins. In addition, PIP2 controls the apical and lateral localization of Crag (Calmodulin-binding protein related to a Rab3 GDP/GTP exchange protein), a factor specifically required to prevent aberrant apical secretion of BM. We propose that PIP2, through the control of Crag's subcellular localization, restricts the secretion of BM proteins to the basal side. </p> |
DOI | 10.1073/pnas.1407351111 |
Alternate Journal | Proc Natl Acad Sci U S A |
PubMed ID | 24828534 |
PubMed Central ID | PMC4040573 |
Grant List | R01 GM077620 / GM / NIGMS NIH HHS / United States / HHMI / Howard Hughes Medical Institute / United States |