Spines and neurite branches function as geometric attractors that enhance protein kinase C action.
Ca2+ and diacylglycerol-regulated protein kinase Cs (PKCs; conventional PKC isoforms, such as PKCgamma) are multifunctional signaling molecules that undergo reversible plasma membrane translocation as part of their mechanism of activation. In this article, we investigate PKCgamma translocation in hippocampal neurons and show that electrical or glutamate stimulation leads to a striking enrichment of PKCgamma in synaptic spines and dendritic branches. Translocation into spines and branches was delayed when compared with the soma plasma membrane, and PKCgamma remained in these structures for a prolonged period after the response in the soma ceased. We have developed a quantitative model for the translocation process by measuring the rate at which PKCgamma crossed the neck of spines, as well as cytosolic and membrane diffusion coefficients of PKCgamma. Our study suggests that neurons make use of a high surface-to-volume ratio of spines and branches to create a geometric attraction process for PKC that imposes a delayed enhancement of PKC action at synapses and in peripheral processes.
Craske
Madeleine L
ML
Department of Molecular Pharmacology, Stanford University School of Medicine, Stanford, CA 94305, USA.
Fivaz
Marc
M
Batada
Nizar N
NN
Meyer
Tobias
T
D000818:Animals; D001692:Biological Transport; D020013:Calcium Signaling; D002462:Cell Membrane / Q000737:chemistry; D002478:Cells, Cultured; D003600:Cytosol / Q000737:chemistry; D004247:DNA / Q000235:genetics; D049229:Dendritic Spines / Q000737:chemistry / Q000201:enzymology*; D018698:Glutamic Acid / Q000494:pharmacology; D026901:Membrane Transport Proteins / Q000032:analysis / Q000378:metabolism; D018613:Microscopy, Confocal; D008954:Models, Biological; D016501:Neurites / Q000737:chemistry / Q000201:enzymology*; D038761:Photobleaching; D011493:Protein Kinase C / Q000032:analysis / Q000235:genetics / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013997:Time Factors
D026901:Membrane Transport Proteins; D018698:Glutamic Acid; D004247:DNA; C087857:protein kinase C gamma; D011493:Protein Kinase C