RGD Reference Report - Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry. - Rat Genome Database

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Insights into the residence in lipid rafts of adenylyl cyclase AC8 and its regulation by capacitative calcium entry.

Authors: Pagano, Mario  Clynes, Michael A  Masada, Nanako  Ciruela, Antonio  Ayling, Laura-Jo  Wachten, Sebastian  Cooper, Dermot M F 
Citation: Pagano M, etal., Am J Physiol Cell Physiol. 2009 Mar;296(3):C607-19. doi: 10.1152/ajpcell.00488.2008. Epub 2009 Jan 21.
RGD ID: 13800545
Pubmed: PMID:19158400   (View Abstract at PubMed)
PMCID: PMC2660271   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpcell.00488.2008   (Journal Full-text)

Adenylyl cyclases (ACs) are a family of critically important signaling molecules that are regulated by multiple pathways. Adenylyl cyclase 8 (AC8) is a Ca(2+) stimulated isoform that displays a selective regulation by capacitative Ca(2+) entry (CCE), the process whereby the entry of Ca(2+) into cells is triggered by the emptying of intracellular stores. This selectivity was believed to be achieved through the localization of AC8 in lipid raft microdomains, along with components of the CCE apparatus. In the present study, we show that an intact leucine zipper motif is required for the efficient N-linked glycosylation of AC8, and that this N-linked glycosylation is important to target AC8 into lipid rafts. Disruption of the leucine zipper by site-directed mutagenesis results in the elimination of N-glycosylated forms and their exclusion from lipid rafts. Mutants of AC8 that cannot be N-glycosylated are not demonstrably associated with rafts, although they can still be regulated by CCE; however, raft integrity is required for the regulation of these mutants. These findings suggest that raft localized proteins in addition to AC8 are needed to mediate its regulation by CCE.



Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adcy8Ratcellular response to calcium ion involved_inIDA PMID:19158400UniProt 
Adcy8Ratprotein complex oligomerization involved_inIDA PMID:19158400UniProt 

Cellular Component

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adcy8Ratclathrin-coated pit located_inIDA PMID:19158400UniProt 
Adcy8Ratmembrane raft located_inIDA PMID:19158400UniProt 

Molecular Function

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
Adcy8Ratcalcium- and calmodulin-responsive adenylate cyclase activity enablesIDA PMID:19158400UniProt 
Adcy8Ratprotein dimerization activity enablesIDA PMID:19158400UniProt 
Adcy8Ratprotein homodimerization activity enablesIDA PMID:19158400UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Adcy8  (adenylate cyclase 8)


Additional Information