Pathways that control cortical F-actin dynamics during secretion.
Chromaffin cells possess a mesh of filamentous actin underneath the plasma membrane which acts as a barrier to the chromaffin vesicles access to exocytotic sites. Disassembly of cortical F-actin in response to stimulation allows the movement of vesicles from the reserve pool to the release-ready vesicle pool and, therefore, to exocytotic sites. The dynamics of cortical F-actin is controlled by two mechanisms: a) stimulation-induced Ca2+ entry and scinderin activation and b) protein kinase C (PKC) activation and MARCKS phosphorylation as demonstrated here by experiments with recombinant proteins, antisense olygodeoxynucleotides and vector mediated transient expressions. Under physiological conditions (i.e., cholinergic receptor stimulation followed by Ca2+ entry), mechanism (a) is the most important for the control of cortical F-actin network whereas when Ca2+ is released from intracellular stores (i.e., histamine stimulation) cortical F-actin is regulated mainly by mechanism b.
Trifaró
J M
JM
Secretory Process Research Program, Department of Cellular and Molecular Medicine, Faculty of Medicine, University of Ottawa, Ontario, Canada K1H 8M5. jtrifaro@uottawa.ca
Lejen
T
T
Rosé
S D
SD
Pene
T Dumitrescu
TD
Barkar
N D
ND
Seward
E P
EP
D000199:Actins / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins; D002540:Cerebral Cortex / Q000201:enzymology / Q000378:metabolism*; D004789:Enzyme Activation; D018260:Gelsolin; D005959:Glucosidases; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D008840:Microfilament Proteins / Q000378:metabolism; D008969:Molecular Sequence Data; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D010750:Phosphoproteins / Q000378:metabolism; D011493:Protein Kinase C / Q000378:metabolism
D000199:Actins; D002135:Calcium-Binding Proteins; D018260:Gelsolin; D047908:Intracellular Signaling Peptides and Proteins; C000619710:MARCKS protein, human; D008565:Membrane Proteins; D008840:Microfilament Proteins; D010750:Phosphoproteins; C065395:scinderin; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D011493:Protein Kinase C; D005959:Glucosidases; C070368:PRKCSH protein, human; D002118:Calcium