Classical protein kinase C(s) regulates targeting of synaptotagmin IX to the endocytic recycling compartment.
Neuronal and non-neuronal tissues show distinctly different intracellular localization of synaptotagmin (Syt) homologues. Therefore, cell type-specific mechanisms are likely to direct Syt homologues to their final cellular destinations. Syt IX localizes to dense core vesicles in PC12 cells. However, in the rat basophilic leukemia (RBL-2H3) mast cell line, as well as in CHO cells, Syt IX is localized at the endocytic recycling compartment (ERC). We show that targeting of Syt IX to the ERC involves constitutive trafficking to the plasma membrane followed by internalization and transport to the ERC. We further show that internalization from the plasma membrane and delivery to the ERC are dependent on phosphorylation by Ca(2+)-dependent protein kinase Calpha or beta. As such, correct targeting of Syt IX is facilitated by the phorbol ester TPA but prevented by the cPKC inhibitor Go 6976.
Haberman
Yael
Y
Department of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Ziv
Idit
I
Gorzalczany
Yaara
Y
Fukuda
Mitsunori
M
Sagi-Eisenberg
Ronit
R
D000818:Animals; D016466:CHO Cells; D002135:Calcium-Binding Proteins / Q000378:metabolism*; D002451:Cell Compartmentation / Q000187:drug effects / Q000502:physiology; D045744:Cell Line, Tumor; D002462:Cell Membrane / Q000378:metabolism*; D006224:Cricetinae; D004705:Endocytosis / Q000187:drug effects / Q000502:physiology*; D011992:Endosomes / Q000378:metabolism*; D004791:Enzyme Inhibitors / Q000494:pharmacology; D000090204:Mesothelin; D010703:Phorbol Esters / Q000494:pharmacology; D010766:Phosphorylation / Q000187:drug effects; D011493:Protein Kinase C / Q000037:antagonists & inhibitors / Q000378:metabolism*; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D021381:Protein Transport / Q000187:drug effects / Q000502:physiology; D051381:Rats; D050857:Synaptotagmins; D022161:Transport Vesicles / Q000378:metabolism*
D002135:Calcium-Binding Proteins; D004791:Enzyme Inhibitors; C000715529:Msln protein, rat; D010703:Phorbol Esters; C483193:Syt9 protein, rat; D050857:Synaptotagmins; D011493:Protein Kinase C; D064546:Protein Kinase C beta; D051571:Protein Kinase C-alpha; D000090204:Mesothelin