Open AccessAlternative Splicing and Cleavage of GLUT8
Author(s) -
Caroline M. Alexander,
Jack A. Martin,
Elias Oxman,
Ildikó Kasza,
Katherine A Senn,
Heidi Dvinge
Publication year - 2021
Publication title -
molecular and cellular biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.14
H-Index - 327
eISSN - 1067-8824
pISSN - 0270-7306
DOI - 10.1128/mcb.00480-20
Subject(s) - biology , endosome , microbiology and biotechnology , glut1 , alternative splicing , rna splicing , population , glucose transporter , messenger rna , biochemistry , gene , rna , endocrinology , demography , sociology , insulin , intracellular
The GLUT ( SLC2 ) family of membrane-associated transporters are described as glucose transporters. However, this family is divided into three classes and, though the regulated transporter activity of class I proteins is becoming better understood, class III protein functions continue to be obscure. We have cataloged the relative expression and splicing of SLC2 mRNA isomers in tumors and normal tissues, with a focus on breast tumors and cell lines. mRNA for the class III protein GLUT8 is the predominant SLC2 species expressed alongside GLUT1 in many tissues, but GLUT8 mRNA exists mostly as an untranslated splice form in tumors. We confirm that GLUT8 is not presented at the cell surface and does not transport glucose directly. However, we reveal a lysosome-dependent reaction that cleaves the GLUT8 protein and releases the carboxy-terminal peptide to a separate vesicle population. Given the localization of GLUT8 at a major metabolic hub (the late endosomal/lysosomal interface) and its regulated cleavage reaction, we evaluated TXNIP-mediated hexosamine homeostasis and speculate that GLUT8 may function as a sensory component of this reaction.