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PMID: 22699897 Published · ppublish English Journal Article Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't

Cyclin-dependent kinase 5 regulates the polarized trafficking of neuropeptide-containing dense-core vesicles in Caenorhabditis elegans motor neurons.

The Journal of neuroscience : the official journal of the Society for Neuroscience ·Vol. 32 ·No. 24 ·2012-06-13 ·Pages 8158-72

Goodwin PR, Sasaki JM, Juo P

Abstract

The polarized trafficking of axonal and dendritic proteins is essential for the structure and function of neurons. Cyclin-dependent kinase 5 (CDK-5) and its activator CDKA-1/p35 regulate diverse aspects of nervous system development and function. Here, we show that CDK-5 and CDKA-1/p35 are required for the polarized distribution of neuropeptide-containing dense-core vesicles (DCVs) in Caenorhabditis elegans cholinergic motor neurons. In cdk-5 or cdka-1/p35 mutants, the predominantly axonal localization of DCVs containing INS-22 neuropeptides was disrupted and DCVs accumulated in dendrites. Time-lapse microscopy in DB class motor neurons revealed decreased trafficking of DCVs in axons and increased trafficking and accumulation of DCVs in cdk-5 mutant dendrites. The polarized distribution of several axonal and dendritic markers, including synaptic vesicles, was unaltered in cdk-5 mutant DB neurons. We found that microtubule polarity is plus-end out in axons and predominantly minus-end out in dendrites of DB neurons. Surprisingly, cdk-5 mutants had increased amounts of plus-end-out microtubules in dendrites, suggesting that CDK-5 regulates microtubule orientation. However, these changes in microtubule polarity are not responsible for the increased trafficking of DCVs into dendrites. Genetic analysis of cdk-5 and the plus-end-directed axonal DCV motor unc-104/KIF1A suggest that increased trafficking of UNC-104 into dendrites cannot explain the dendritic DCV accumulation. Instead, we found that mutations in the minus-end-directed motor cytoplasmic dynein, completely block the increased DCVs observed in cdk-5 mutant dendrites without affecting microtubule polarity. We propose a model in which CDK-5 regulates DCV polarity by both promoting DCV trafficking in axons and preventing dynein-dependent DCV trafficking into dendrites.

MeSH Terms
Animals Animals, Genetically Modified Axons/metabolism,ultrastructure Caenorhabditis elegans Caenorhabditis elegans Proteins/metabolism,physiology Cholinergic Neurons/metabolism Cyclin-Dependent Kinase 5/genetics,physiology Dendrites/metabolism,ultrastructure Dyneins/genetics,physiology Microtubules/ultrastructure Motor Neurons/metabolism Mutation/physiology Nerve Tissue Proteins/genetics,metabolism,physiology Protein Transport/physiology Secretory Vesicles/metabolism,ultrastructure
Chemicals
Caenorhabditis elegans Proteins Nerve Tissue Proteins UNC-104 protein, C elegans neuronal Cdk5 activator (p25-p35) Cyclin-Dependent Kinase 5 Dyneins
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Goodwin Patricia R
Department of Molecular Physiology and Pharmacology, Sackler School of Graduate Biomedical Sciences, Tufts University School of Medicine, Boston, Massachusetts 02111, USA.
Sasaki Jennifer M
Juo Peter
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Article Info
Journal
The Journal of neuroscience : the official journal of the Society for Neuroscience
Abbr.
J Neurosci
ISSN
1529-2401
DOI
10.1523/JNEUROSCI.0251-12.2012
Published
2012-06-13
Pages
8158-72
Language
English
Region
United States
NLM ID
8102140
PMCID
PMC3392131
Subset
IM
Grants
NINDS NIH HHS · R56 NS059953 · United States
NINDS NIH HHS · R01 NS059953 · United States
NINDS NIH HHS · T32 NS061764 · United States
NINDS NIH HHS · NS059953 · United States
NINDS NIH HHS · P30 NS047243 · United States
External Links
PubMed source DOI: 10.1523/JNEUROSCI.0251-12.2012 PMC Full Text View journal details
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