PTEN Regulates Glucose Transporter Recycling by Impairing SNX27 Retromer Assembly

Shinde, Swapnil Rohidas (2017) PTEN Regulates Glucose Transporter Recycling by Impairing SNX27 Retromer Assembly. Cell Reports, 21. pp. 1655-1666.

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The tumor suppressor PTEN executes cellular func-tions predominantly through its phosphatase activ-ity. Here we identified a phosphatase-independent role for PTEN during vesicular trafficking of the glucose transporter GLUT1. PTEN physically inter-acts with SNX27, a component of the retromer com-plex that recycles transmembrane receptors such as GLUT1 from endosomes to the plasma membrane.PTEN binding with SNX27 prevents GLUT1 accumu-lation at the plasma membrane because of defective recycling and thus reduces cellular glucose uptake.Mechanistically, PTEN blocks the association of SNX27 with VPS26 and thereby hinders assembly of a functional retromer complex during the receptor recycling process. Importantly, we found a PTEN so-matic mutation (T401I) that is defective in disrupting the association between SNX27 and VPS26, sug- gesting a critical role for PTEN in controlling optimal GLUT1 levels at the membrane to prevent tumor pro-gression. Together, our results reveal a fundamental role of PTEN in the regulation of the SNX27 retromer pathway, which governs glucose transport and might contribute to PTEN tumor suppressor function

Item Type: Article
Subjects: Research > Research Center - Health Sciences
Depositing User: KMC Library
Date Deposited: 06 Aug 2019 03:56
Last Modified: 06 Aug 2019 03:56

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