title: PKC-induced intracellular trafficking of Ca(V)2 precedes its rapid recruitment to the plasma membrane.
abstract: Activation of protein kinase C (PKC) potentiates secretion in Aplysia peptidergic neurons, in part by inducing new sites for peptide release at growth cone terminals. The mechanisms by which ion channels are trafficked to such sites are, however, not well understood. We now show that PKC activation rapidly recruits new Ca(V)2 subunits to the plasma membrane, and that recruitment is blocked by latrunculin B, an inhibitor of actin polymerization. In contrast, inhibition of microtubule polymerization selectively prevents the appearance of Ca(V)2 subunits only at the distal edge of the growth cone. In resting neurons, Ca(V)2-containing organelles reside in the central region of growth cones, but are absent from distal lamellipodia. After activation of PKC, these organelles are transported on microtubules to the lamellipodium. The ability to traffic to the most distal sites of channel insertion inside the lamellipodium does, therefore, not require intact actin but requires intact microtubules. Only after activation of PKC do Ca(V)2 channels associate with actin and undergo insertion into the plasma membrane.
authors.affiliation: Department of Pharmacology, Section of Endocrinology, Yale School of Medicine, New Haven, Connecticut 06520, USA.
authors.forename: Yalan
authors.initials: Y
authors.lastname: Zhang
authors.forename: Jessica S
authors.initials: JS
authors.lastname: Helm
authors.forename: Adriano
authors.initials: A
authors.lastname: Senatore
authors.forename: J David
authors.initials: JD
authors.lastname: Spafford
authors.forename: Leonard K
authors.initials: LK
authors.lastname: Kaczmarek
authors.forename: Elizabeth A
authors.initials: EA
authors.lastname: Jonas
mesh_terms: D000818:Animals; D001048:Aplysia; D015220:Calcium Channels / Q000378:metabolism*; D020864:Calcium Channels, N-Type / Q000378:metabolism*; D002462:Cell Membrane / Q000378:metabolism*; D002478:Cells, Cultured; D004789:Enzyme Activation / Q000502:physiology; D007424:Intracellular Fluid / Q000502:physiology*; D011493:Protein Kinase C / Q000502:physiology*; D021122:Protein Subunits / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
chemical_list: D015220:Calcium Channels; D020864:Calcium Channels, N-Type; D021122:Protein Subunits; D011493:Protein Kinase C