N-sulfation of heparan sulfate is critical for syndecan-4 mediated podocyte cell-matrix interactions.

N-sulfation of heparan sulfate is critical for syndecan-4 mediated podocyte cell-matrix interactions. Am J Physiol Renal Physiol. 2016 Mar 2;:ajprenal.00603.2015 Authors: Sugar T, Wassenhove-McCarthy DJ, Orr AW, Green J, van Kuppevelt TH, McCarthy KJ Abstract Previous work showed that podocytes unable to assemble heparan sulfate on cell surface proteoglycan core proteins have compromised cell-matrix interactions. This present report further explores the role of N-sulfation of intact heparan chains in podocyte-matrix interactions. For the purposes of this study, a murine model in which the enzyme, N-deacetylase/N-sulfotransferase 1 (NDST1) was specifically deleted in podocytes and immortalized podocyte cell lines lacking NDST1 were developed and used to explore the effects of such a mutation on podocyte behavior in vitro. NDST1 is a bifunctional enzyme, ultimately responsible for N-sulfation of heparan glycosaminoglycans produced by cells. Immunostaining of glomeruli from mice whose podocytes were null for Ndst1 (Ndst1(-/-)) showed a disrupted pattern of localization for the cell surface proteoglycan, syndecan-4 and for α-actinin-4 when compared to controls. The pattern of immunostaining for synaptopodin and nephrin did not show as significant alterations. In vitro studies showed that Ndst1(-/-) podocytes attached, spread and migrated less efficiently compared to Ndst1+/+ podocytes. Immunostaining in vitro for several markers for mol...
Source: Am J Physiol Renal P... - Category: Urology & Nephrology Authors: Tags: Am J Physiol Renal Physiol Source Type: research