Protein kinase D promotes plasticity-induced F-actin stabilization in dendritic spines and regulates memory formation

• Published in: The Journal of cell biology Vol. 210; no. 5; pp. 771 - 783
• Main Authors: Bencsik, Norbert, Szíber, Zsófia, Liliom, Hanna, Tárnok, Krisztián, Borbély, Sándor, Gulyás, Márton, Rátkai, Anikó, Szűcs, Attila, Hazai-Novák, Diána, Ellwanger, Kornelia, Rácz, Bence, Pfizenmaier, Klaus, Hausser, Angelika, Schlett, Katalin
• Format: Journal Article
• Language: English
• Published: United States Rockefeller University Press 31.08.2015; The Rockefeller University Press
• Subjects: Actins - metabolism; Animals; CA1 Region, Hippocampal - cytology; CA1 Region, Hippocampal - metabolism; CA2 Region, Hippocampal - cytology; CA2 Region, Hippocampal - metabolism; Cell Survival; Cells, Cultured; Dendritic cells; Dendritic Spines - metabolism; Glycine - pharmacology; Green Fluorescent Proteins - metabolism; Kinases; Learning - physiology; Long-Term Potentiation - drug effects; Long-Term Potentiation - physiology; Memory; Memory - physiology; Mice; Mice, Transgenic; Morphology; Neuromuscular Depolarizing Agents - pharmacology; Neuronal Plasticity - physiology; Patch-Clamp Techniques; Potassium Chloride - pharmacology; Protein Kinase C - biosynthesis; Protein Kinase C - metabolism; Spine
• ISSN: 0021-9525; 1540-8140
• DOI: 10.1083/jcb.201501114

Actin turnover in dendritic spines influences spine development, morphology, and plasticity, with functional consequences on learning and memory formation. In nonneuronal cells, protein kinase D (PKD) has an important role in stabilizing F-actin via multiple molecular pathways. Using in vitro models of neuronal plasticity, such as glycine-induced chemical long-term potentiation (LTP), known to evoke synaptic plasticity, or long-term depolarization block by KCl, leading to homeostatic morphological changes, we show that actin stabilization needed for the enlargement of dendritic spines is dependent on PKD activity. Consequently, impaired PKD functions attenuate activity-dependent changes in hippocampal dendritic spines, including LTP formation, cause morphological alterations in vivo, and have deleterious consequences on spatial memory formation. We thus provide compelling evidence that PKD controls synaptic plasticity and learning by regulating actin stability in dendritic spines.