PKM zeta restricts dendritic arbor growth by filopodial and branch stabilization within the intact and awake developing brain.
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.
Liu
Xue Feng
XF
Department of Cellular and Physiological Sciences, University of British Columbia, Graduate Program in Neuroscience, Brain Research Centre, Vancouver, British Columbia V6T 2B5, Canada.
Tari
Parisa Karimi
PK
Haas
Kurt
K
D000595:Amino Acid Sequence; D000818:Animals; D001921:Brain / Q000196:embryology* / Q000201:enzymology; D003712:Dendrites / Q000201:enzymology*; D051379:Mice; D008969:Molecular Sequence Data; D055495:Neurogenesis / Q000502:physiology; D009473:Neuronal Plasticity / Q000502:physiology; D011493:Protein Kinase C / Q000502:physiology*; D011554:Pseudopodia / Q000201:enzymology*; D013477:Superior Colliculi / Q000201:enzymology / Q000254:growth & development; D014851:Wakefulness / Q000502:physiology*; D029867:Xenopus Proteins / Q000502:physiology*; D014982:Xenopus laevis; D000099221:Protein Kinase C zeta
D011493:Protein Kinase C; D029867:Xenopus Proteins; D000099221:Protein Kinase C zeta