A unique spacer domain of synaptotagmin IV is essential for Golgi localization

Mitsunori Fukuda, Keiji Ibata, Katsuhiko Mikoshiba

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Synaptotagmin (Syt) family members consist of six separate domains: a short amino terminus, a single transmembrane domain, a spacer domain, a C2A domain, a C2B domain and a short carboxyl (C) terminus. Despite sharing the same domain structures, several synaptotagmin isoforms shew distinct subcellular localization. Syt IV is mainly localized at the Golgi, while Syt I, a possible Ca2+-sensor for secretory vesicles, is localized at dense-core vesicles and synaptic-like microvesicles in PC12 cells. In this study, we sought to identify the region responsible for the Golgi localization of Syt IV by immunocytochemical and biochemical analyses as a means of defining the distinct subcellular localization of the synaptotagmin family. We found that the unique C-terminus of the spacer domain (amino acid residues 73-144) between the transmembrane domain and the C2A domain is essential for the Golgi localization of Syt IV. In addition, the short C-terminus is probably involved in proper folding of the protein, especially the C2B domain. Without the C-terminus, Syt IVΔC proteins are not targeted to the Golgi and seem to colocalize with an endoplasmic reticulum (ER) marker (i.e. induce crystalloid ER-like structures). On the basis of these results, we propose that the divergent spacer domain among synaptotagmin isoforms may contain certain signals that determine the final destination of each isoform.

Original languageEnglish
Pages (from-to)730-740
Number of pages11
JournalJournal of Neurochemistry
Volume77
Issue number3
DOIs
Publication statusPublished - 2001
Externally publishedYes

Fingerprint

Synaptotagmins
Protein Isoforms
Secretory Vesicles
Endoplasmic Reticulum
Synaptotagmin I
PC12 Cells
Protein Folding
Proteins
Amino Acids

Keywords

  • C2 domain
  • Exocytosis
  • Glycosylation
  • Golgi
  • Immediate early genes
  • Synaptotagmin

ASJC Scopus subject areas

  • Biochemistry
  • Cellular and Molecular Neuroscience

Cite this

A unique spacer domain of synaptotagmin IV is essential for Golgi localization. / Fukuda, Mitsunori; Ibata, Keiji; Mikoshiba, Katsuhiko.

In: Journal of Neurochemistry, Vol. 77, No. 3, 2001, p. 730-740.

Research output: Contribution to journalArticle

Fukuda, Mitsunori ; Ibata, Keiji ; Mikoshiba, Katsuhiko. / A unique spacer domain of synaptotagmin IV is essential for Golgi localization. In: Journal of Neurochemistry. 2001 ; Vol. 77, No. 3. pp. 730-740.
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