RGD Reference Report - Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons. - Rat Genome Database

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Doublecortin microtubule affinity is regulated by a balance of kinase and phosphatase activity at the leading edge of migrating neurons.

Authors: Schaar, BT  Kinoshita, K  McConnell, SK 
Citation: Schaar BT, etal., Neuron. 2004 Jan 22;41(2):203-13.
RGD ID: 8554024
Pubmed: PMID:14741102   (View Abstract at PubMed)

Doublecortin (Dcx) is a microtubule-associated protein that is mutated in X-linked lissencephaly (X-LIS), a neuronal migration disorder associated with epilepsy and mental retardation. Although Dcx can bind ubiquitously to microtubules in nonneuronal cells, Dcx is highly enriched in the leading processes of migrating neurons and the growth cone region of differentiating neurons. We present evidence that Dcx/microtubule interactions are negatively controlled by Protein Kinase A (PKA) and the MARK/PAR-1 family of protein kinases. In addition to a consensus MARK site, we identified a serine within a novel sequence that is crucial for the PKA- and MARK-dependent regulation of Dcx's microtubule binding activity in vitro. This serine is mutated in two families affected by X-LIS. Immunostaining neurons with an antibody that recognizes phosphorylated substrates of MARK supports the conclusion that Dcx localization and function are regulated at the leading edge of migrating cells by a balance of kinase and phosphatase activity.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
neuron migration involved_inIDA 8554024; 8554024PMID:14741102UniProt 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
membrane located_inIDA 8554024PMID:14741102UniProt 

Molecular Function
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
protein binding enablesIPIUniProtKB:O436028554024PMID:14741102UniProt 
protein serine/threonine kinase activity enablesIDA 8554024; 8554024PMID:14741102UniProt 

Objects Annotated

Genes (Rattus norvegicus)
Mark1  (microtubule affinity regulating kinase 1)
Mark2  (microtubule affinity regulating kinase 2)


Additional Information