PKM zeta restricts dendritic arbor growth by filopodial and branch stabilization within the intact and awake developing brain.

TitlePKM zeta restricts dendritic arbor growth by filopodial and branch stabilization within the intact and awake developing brain.
Publication TypeJournal Article
Year of Publication2009
AuthorsLiu XFeng, Tari PKarimi, Haas K
JournalJ Neurosci
Volume29
Issue39
Pagination12229-35
Date Published2009 Sep 30
ISSN1529-2401
KeywordsAmino Acid Sequence, Animals, Brain, Dendrites, Mice, Molecular Sequence Data, Neurogenesis, Neuronal Plasticity, Protein Kinase C, Pseudopodia, Superior Colliculi, Wakefulness, Xenopus laevis, Xenopus Proteins
Abstract

The molecular mechanisms underlying activity-dependent neural circuit growth and plasticity during early brain development remain poorly understood. Protein kinase Mzeta (PKMz), an endogenous constitutively active kinase associated with late-phase long-term synaptic potentiation and memory in the mature brain, is expressed in the embryonic Xenopus retinotectal system with heightened levels during peak periods of dendrite growth and synaptogenesis. In vivo rapid time-lapse imaging of actively growing tectal neurons and comprehensive three-dimensional tracking of dynamic dendritic growth behavior finds that altered PKMz activity affects morphologic stabilization. Exogenous expression of PKMz within single neurons stabilizes dendritic filopodia by increasing dendritic filopodial lifetimes and decreasing filopodial additions, eliminations, and motility, whereas long-term in vivo imaging demonstrates restricted expansion of the dendritic arbor. Alternatively, blocking endogenous PKMz activity in individual growing tectal neurons with an inhibitory peptide (zeta-inhibitory peptide) destabilizes dendritic filopodia and over long periods promotes excessive arbor expansion. Furthermore, inhibiting endogenous PKMz throughout the tectum decreases colocalization of immunostained presynaptic and postsynaptic markers, SNAP-25 and PSD-95, respectively, suggesting impaired synapse maintenance. Together, these results implicate PKMz activity in restricting dendritic arborization during embryonic brain circuit development through synaptotropic stabilization of dynamic processes.

URLhttps://www.ncbi.nlm.nih.gov/pubmed/19793981
DOI10.1523/JNEUROSCI.2842-09.2009
Alternate JournalJ. Neurosci.
PubMed ID19793981