These tools will no longer be maintained as of December 31, 2024. Archived website can be found here. PubMed4Hh GitHub repository can be found here. Contact NLM Customer Service if you have questions.


Pubmed for Handhelds

PUBMED FOR HANDHELDS

Search MEDLINE/PubMed

  • Title: The evolutionary pressure to inactivate. A subclass of synaptotagmins with an amino acid substitution that abolishes Ca2+ binding.
    Author: von Poser C, Ichtchenko K, Shao X, Rizo J, Südhof TC.
    Journal: J Biol Chem; 1997 May 30; 272(22):14314-9. PubMed ID: 9162066.
    Abstract:
    Synaptotagmin I is a Ca2+-binding protein of synaptic vesicles that serves as a Ca2+ sensor for neurotransmitter release and was the first member found of a large family of trafficking proteins. We have now identified a novel synaptotagmin, synaptotagmin XI, that is highly expressed in brain and at lower levels in other tissues. Like other synaptotagmins, synaptotagmin XI has a single transmembrane region and two cytoplasmic C2-domains but is most closely related to synaptotagmin IV with which it forms a new subclass of synaptotagmins. The first C2-domain of synaptotagmin I (the C2A-domain) binds phospholipids as a function of Ca2+ and contains a Ca2+-binding site, the C2-motif, that binds at least two Ca2+ ions via five aspartate residues and is conserved in most C2-domains (Shao, X., Davletov, B., Sutton, B., Südhof, T. C., Rizo, J. R. (1996) Science 273, 248-253). In the C2A-domains of synaptotagmins IV and XI, however, one of the five Ca2+-binding aspartates in the C2-motif is substituted for a serine, suggesting that these C2-domains do not bind Ca2+. To test this, we produced recombinant C2A-domains from synaptotagmins IV and XI with either wild type serine or mutant aspartate in the C2-motif. Circular dichroism showed that Ca2+ stabilizes both mutant but not wild type C2-domains against temperature-induced denaturation, indicating that the mutations restore Ca2+-binding to the wild type C2-domains. Furthermore, wild type C2A-domains of synaptotagmins IV and XI exhibited no Ca2+-dependent phospholipid binding, whereas mutant C2A-domains bound phospholipids as a function of Ca2+ similarly to wild type synaptotagmin I. These experiments suggest that a class of synaptotagmins was selected during evolution in which the Ca2+-binding site of the C2A-domain was inactivated by a single point mutation. Thus, synaptotagmins must have Ca2+-independent functions as well as Ca2+-dependent functions that are selectively maintained in distinct members of this gene family.
    [Abstract] [Full Text] [Related] [New Search]