RGD Reference Report - Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1. - Rat Genome Database

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Huntingtin and huntingtin-associated protein 1 influence neuronal calcium signaling mediated by inositol-(1,4,5) triphosphate receptor type 1.

Authors: Tang, TS  Tu, H  Chan, EY  Maximov, A  Wang, Z  Wellington, CL  Hayden, MR  Bezprozvanny, I 
Citation: Tang TS, etal., Neuron. 2003 Jul 17;39(2):227-39.
RGD ID: 6482800
Pubmed: PMID:12873381   (View Abstract at PubMed)
PMCID: PMC3220623   (View Article at PubMed Central)

Huntington's disease (HD) is caused by polyglutamine expansion (exp) in huntingtin (Htt). The type 1 inositol (1,4,5)-triphosphate receptor (InsP3R1) is an intracellular calcium (Ca2+) release channel that plays an important role in neuronal function. In a yeast two-hybrid screen with the InsP3R1 carboxy terminus, we isolated Htt-associated protein-1A (HAP1A). We show that an InsP3R1-HAP1A-Htt ternary complex is formed in vitro and in vivo. In planar lipid bilayer reconstitution experiments, InsP3R1 activation by InsP3 is sensitized by Httexp, but not by normal Htt. Transfection of full-length Httexp or caspase-resistant Httexp, but not normal Htt, into medium spiny striatal neurons faciliates Ca2+ release in response to threshold concentrations of the selective mGluR1/5 agonist 3,5-DHPG. Our findings identify a novel molecular link between Htt and InsP3R1-mediated neuronal Ca2+ signaling and provide an explanation for the derangement of cytosolic Ca2+ signaling in HD patients and mouse models.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Hap1Ratpositive regulation of inositol 1,4,5-trisphosphate-sensitive calcium-release channel activity involved_inIDA PMID:12873381UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Epb41l1  (erythrocyte membrane protein band 4.1-like 1)
Hap1  (huntingtin-associated protein 1)
Htt  (huntingtin)
Itpr1  (inositol 1,4,5-trisphosphate receptor, type 1)


Additional Information