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O-GlcNAcylation suppresses the ion current IClswell by preventing the binding of the protein ICln to α-integrin

ABSTRACT: Here we show that experimentally increased O-GlcNAcylation of cellular proteins inhibited the endogenous as well as the ICln-induced IClswell current and prevented RVD in a human renal cell line, while decreases in O-GlcNAcylation augmented the current magnitude. In parallel, increases or decreases in O-GlcNAcylation respectively weakened or stabilized the binding of ICln to the intracellular domain of α-integrin, a process that is essential for the activation of IClswell. Mutation of the putative Yin-O-Yang site at Ser67 rendered the ICln-induced IClswell current unresponsive to O-GlcNAc variations, and the ICln interaction with α-integrin insensitive to O-GlcNAcylation. In addition, exposure of cells to a hypotonic solution reduced the O-GlcNAcylation of cellular proteins. Together, these findings show that O-GlcNAcylation affects RVD by influencing IClswell, and further indicate that hypotonicity may activate IClswell by reducing the O-GlcNAcylation of ICln at Ser67, therefore permitting its binding to α-integrin. We propose that disturbances in the regulation of cellular volume may contribute to disease in settings of chronically elevated O-GlcNAcylation, including diabetic nephropathy.

ORGANISM(S): Homo Sapiens (human)

SUBMITTER: Dr. Silvia Dossena

PROVIDER: PXD022389 | JPOST Repository | Fri Nov 06 00:00:00 GMT 2020

REPOSITORIES: jPOST

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			Action	DRS
	170904-PTE-GLNAC-1%20(F001619).mzid	Mzid
	170904-PTE-GLNAC-1%20(F001619).mzid_170904-PTE-GLNAC-1_(F001619).MGF	Mzid
	170904-PTE-GLNAC-1.mgf	Mgf
	170904-PTE-GLNAC-1.raw	Raw

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O-GlcNAcylation of human TATA-Box binding protein is required to sustain key metabolic enzyme gene expression

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