RGD Reference Report - Identification of synaptotagmin effectors via acute inhibition of secretion from cracked PC12 cells. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Identification of synaptotagmin effectors via acute inhibition of secretion from cracked PC12 cells.

Authors: Tucker, WC  Edwardson, JM  Bai, J  Kim, HJ  Martin, TF  Chapman, ER 
Citation: Tucker WC, etal., J Cell Biol. 2003 Jul 21;162(2):199-209. Epub 2003 Jul 14.
RGD ID: 11079189
Pubmed: (View Article at PubMed) PMID:12860971
DOI: Full-text: DOI:10.1083/jcb.200302060

The synaptotagmins (syts) are a family of membrane proteins proposed to regulate membrane traffic in neuronal and nonneuronal cells. In neurons, the Ca2+-sensing ability of syt I is critical for fusion of docked synaptic vesicles with the plasma membrane in response to stimulation. Several putative Ca2+-syt effectors have been identified, but in most cases the functional significance of these interactions remains unknown. Here, we have used recombinant C2 domains derived from the cytoplasmic domains of syts I-XI to interfere with endogenous syt-effector interactions during Ca2+-triggered exocytosis from cracked PC12 cells. Inhibition was closely correlated with syntaxin-SNAP-25 and phosphatidylinositol 4,5-bisphosphate (PIP2)-binding activity. Moreover, we measured the expression levels of endogenous syts in PC12 cells; the major isoforms are I and IX, with trace levels of VII. As expected, if syts I and IX function as Ca2+ sensors, fragments from these isoforms blocked secretion. These data suggest that syts trigger fusion via their Ca2+-regulated interactions with t-SNAREs and PIP2, target molecules known to play critical roles in exocytosis.

Annotation

Gene Ontology Annotations    

Biological Process

Molecular Function

Objects Annotated

Genes (Rattus norvegicus)
Syt1  (synaptotagmin 1)
Syt3  (synaptotagmin 3)


Additional Information