GISP increases neurotransmitter receptor stability by down-regulating ESCRT-mediated lysosomal degradation

S Kantamneni, DA Holman, KA Wilkinson, A Nishimune, JM Henley

Research output: Contribution to journalArticle (Academic Journal)

13 Citations (Scopus)

Abstract

GPCR interacting scaffold protein (GISP) is a multi-domain brain-specific scaffold protein that can regulate GABA(B) receptor complexes by both enhancing their surface expression and by inhibiting their lysosomal degradation. GISP retards degradation of GABA(B) receptors through its interaction with tumour susceptibility gene 101 (TSG101), a member of the endosomal sorting complex required for transport (ESCRT) lysosomal sorting machinery. We show that in addition to GABA(B), GISP exerts a more general role to increase the steady-state levels of several neurotransmitter receptors. Further, GISP delays TSG101-dependent agonist-induced EGFR down-regulation in human embryonic kidney (HEK) 293 cells whereas a mutant GISP lacking the TSG101 binding domain has no effect. These data suggest that GISP acts as a negative regulator of TSG101-dependent lysosomal degradation and plays an important role in determining the availability of neurotransmitter receptors.
Original languageEnglish
Pages (from-to)106 - 110
Number of pages5
JournalNeuroscience Letters
Volume452(2)
DOIs
Publication statusPublished - Mar 2009

Fingerprint Dive into the research topics of 'GISP increases neurotransmitter receptor stability by down-regulating ESCRT-mediated lysosomal degradation'. Together they form a unique fingerprint.

  • Cite this