RGD Reference Report - DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1. - Rat Genome Database

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DISC1 regulates the transport of the NUDEL/LIS1/14-3-3epsilon complex through kinesin-1.

Authors: Taya, S  Shinoda, T  Tsuboi, D  Asaki, J  Nagai, K  Hikita, T  Kuroda, S  Kuroda, K  Shimizu, M  Hirotsune, S  Iwamatsu, A  Kaibuchi, K 
Citation: Taya S, etal., J Neurosci. 2007 Jan 3;27(1):15-26.
RGD ID: 4107038
Pubmed: PMID:17202468   (View Abstract at PubMed)
PMCID: PMC6672274   (View Article at PubMed Central)
DOI: DOI:10.1523/JNEUROSCI.3826-06.2006   (Journal Full-text)

Disrupted-In-Schizophrenia 1 (DISC1) is a candidate gene for susceptibility to schizophrenia. DISC1 is reported to interact with NudE-like (NUDEL), which forms a complex with lissencephaly-1 (LIS1) and 14-3-3epsilon. 14-3-3epsilon is involved in the proper localization of NUDEL and LIS1 in axons. Although the functional significance of this complex in neuronal development has been reported, the transport mechanism of the complex into axons and their functions in axon formation remain essentially unknown. Here we report that Kinesin-1, a motor protein of anterograde axonal transport, was identified as a novel DISC1-interacting molecule. DISC1 directly interacted with kinesin heavy chain of Kinesin-1. Kinesin-1 interacted with the NUDEL/LIS1/14-3-3epsilon complex through DISC1, and these molecules localized mainly at cell bodies and partially in the distal part of the axons. DISC1 partially colocalized with Kinesin family member 5A, NUDEL, LIS1, and 14-3-3epsilon in the growth cones. The knockdown of DISC1 by RNA interference or the dominant-negative form of DISC1 inhibited the accumulation of NUDEL, LIS1, and 14-3-3epsilon at the axons and axon elongation. The knockdown or the dominant-negative form of Kinesin-1 inhibited the accumulation of DISC1 at the axons and axon elongation. Furthermore, the knockdown of NUDEL or LIS1 inhibited axon elongation. Together, these results indicate that DISC1 regulates the localization of NUDEL/LIS1/14-3-3epsilon complex into the axons as a cargo receptor for axon elongation.

Gene Ontology Annotations    Click to see Annotation Detail View

Biological Process
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
positive regulation of axon extension  IMP 4107038; 4107038; 4107038 RGD 

Cellular Component
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
axon  IDA 4107038; 4107038; 4107038; 4107038distalRGD 
cell body  IDA 4107038; 4107038 RGD 
central region of growth cone  IDA 4107038; 4107038; 4107038; 4107038; 4107038 RGD 
kinesin complex  IDA 4107038; 4107038; 4107038; 4107038; 4107038 RGD 
microtubule  IDA 4107038; 4107038 RGD 

Objects Annotated

Genes (Rattus norvegicus)
Disc1  (DISC1 scaffold protein)
Kif5a  (kinesin family member 5A)
Ndel1  (nudE neurodevelopment protein 1-like 1)
Pafah1b1  (platelet-activating factor acetylhydrolase 1b, regulatory subunit 1)
Ywhae  (tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein, epsilon)


Additional Information