Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth

Syann Lee, Christine L. Walker, Barbara Karten, Sharee L. Kuny, Alysa A. Tennese, Megan A. O'Neill, Rachel Wevrick

Research output: Contribution to journalArticle

88 Citations (Scopus)

Abstract

Necdin and Magel2 are related proteins inactivated in Prader-Willi syndrome (PWS), a sporadic chromosomal deletion disorder. We demonstrate that necdin and Magel2 bind to and prevent proteasomal degradation of Fez1, a fasciculation and elongation protein implicated in axonal outgrowth and kinesin-mediated transport, and also bind to the Bardet-Biedl syndrome (BBS) protein BBS4 in co-transfected cells. The interactions among necdin, Magel2, Fez1 and BBS4 occur at or near centrosomes. Centrosomal or pericentriolar dysfunction has previously been implicated in BBS and may also be important in the features of PWS that overlap with BBS, such as learning disabilities, hypogonadism and obesity. Morphological abnormalities in axonal outgrowth and fasciculation manifest in several regions of the nervous system in necdin null mouse embryos, including axons of sympathetic, retinal ganglion cell, serotonergic and catecholaminergic neurons. These data demonstrate that necdin mediates intracellular processes essential for neurite outgrowth and that loss of necdin impinges on axonal outgrowth. We further suggest that loss of necdin contributes to the neurological phenotype of PWS, and raise the possibility that co-deletion of necdin and the related protein Magel2 may explain the lack of single gene mutations in PWS.

Original languageEnglish (US)
Pages (from-to)627-637
Number of pages11
JournalHuman Molecular Genetics
Volume14
Issue number5
DOIs
StatePublished - Mar 1 2005

Fingerprint

Prader-Willi Syndrome
Bardet-Biedl Syndrome
Proteins
Chromosome Disorders
Fasciculation
Serotonergic Neurons
Kinesin
Centrosome
Sympathetic Ganglia
Hypogonadism
necdin
Retinal Ganglion Cells
Learning Disorders
Nervous System
Axons
Embryonic Structures
Obesity
Phenotype
Mutation

ASJC Scopus subject areas

  • Genetics

Cite this

Lee, S., Walker, C. L., Karten, B., Kuny, S. L., Tennese, A. A., O'Neill, M. A., & Wevrick, R. (2005). Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. Human Molecular Genetics, 14(5), 627-637. https://doi.org/10.1093/hmg/ddi059

Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. / Lee, Syann; Walker, Christine L.; Karten, Barbara; Kuny, Sharee L.; Tennese, Alysa A.; O'Neill, Megan A.; Wevrick, Rachel.

In: Human Molecular Genetics, Vol. 14, No. 5, 01.03.2005, p. 627-637.

Research output: Contribution to journalArticle

Lee, S, Walker, CL, Karten, B, Kuny, SL, Tennese, AA, O'Neill, MA & Wevrick, R 2005, 'Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth', Human Molecular Genetics, vol. 14, no. 5, pp. 627-637. https://doi.org/10.1093/hmg/ddi059
Lee, Syann ; Walker, Christine L. ; Karten, Barbara ; Kuny, Sharee L. ; Tennese, Alysa A. ; O'Neill, Megan A. ; Wevrick, Rachel. / Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth. In: Human Molecular Genetics. 2005 ; Vol. 14, No. 5. pp. 627-637.
@article{2c02ad99d78f4ae9888dd1d719548cc4,
title = "Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth",
abstract = "Necdin and Magel2 are related proteins inactivated in Prader-Willi syndrome (PWS), a sporadic chromosomal deletion disorder. We demonstrate that necdin and Magel2 bind to and prevent proteasomal degradation of Fez1, a fasciculation and elongation protein implicated in axonal outgrowth and kinesin-mediated transport, and also bind to the Bardet-Biedl syndrome (BBS) protein BBS4 in co-transfected cells. The interactions among necdin, Magel2, Fez1 and BBS4 occur at or near centrosomes. Centrosomal or pericentriolar dysfunction has previously been implicated in BBS and may also be important in the features of PWS that overlap with BBS, such as learning disabilities, hypogonadism and obesity. Morphological abnormalities in axonal outgrowth and fasciculation manifest in several regions of the nervous system in necdin null mouse embryos, including axons of sympathetic, retinal ganglion cell, serotonergic and catecholaminergic neurons. These data demonstrate that necdin mediates intracellular processes essential for neurite outgrowth and that loss of necdin impinges on axonal outgrowth. We further suggest that loss of necdin contributes to the neurological phenotype of PWS, and raise the possibility that co-deletion of necdin and the related protein Magel2 may explain the lack of single gene mutations in PWS.",
author = "Syann Lee and Walker, {Christine L.} and Barbara Karten and Kuny, {Sharee L.} and Tennese, {Alysa A.} and O'Neill, {Megan A.} and Rachel Wevrick",
year = "2005",
month = "3",
day = "1",
doi = "10.1093/hmg/ddi059",
language = "English (US)",
volume = "14",
pages = "627--637",
journal = "Human Molecular Genetics",
issn = "0964-6906",
publisher = "Oxford University Press",
number = "5",

}

TY - JOUR

T1 - Essential role for the Prader-Willi syndrome protein necdin in axonal outgrowth

AU - Lee, Syann

AU - Walker, Christine L.

AU - Karten, Barbara

AU - Kuny, Sharee L.

AU - Tennese, Alysa A.

AU - O'Neill, Megan A.

AU - Wevrick, Rachel

PY - 2005/3/1

Y1 - 2005/3/1

N2 - Necdin and Magel2 are related proteins inactivated in Prader-Willi syndrome (PWS), a sporadic chromosomal deletion disorder. We demonstrate that necdin and Magel2 bind to and prevent proteasomal degradation of Fez1, a fasciculation and elongation protein implicated in axonal outgrowth and kinesin-mediated transport, and also bind to the Bardet-Biedl syndrome (BBS) protein BBS4 in co-transfected cells. The interactions among necdin, Magel2, Fez1 and BBS4 occur at or near centrosomes. Centrosomal or pericentriolar dysfunction has previously been implicated in BBS and may also be important in the features of PWS that overlap with BBS, such as learning disabilities, hypogonadism and obesity. Morphological abnormalities in axonal outgrowth and fasciculation manifest in several regions of the nervous system in necdin null mouse embryos, including axons of sympathetic, retinal ganglion cell, serotonergic and catecholaminergic neurons. These data demonstrate that necdin mediates intracellular processes essential for neurite outgrowth and that loss of necdin impinges on axonal outgrowth. We further suggest that loss of necdin contributes to the neurological phenotype of PWS, and raise the possibility that co-deletion of necdin and the related protein Magel2 may explain the lack of single gene mutations in PWS.

AB - Necdin and Magel2 are related proteins inactivated in Prader-Willi syndrome (PWS), a sporadic chromosomal deletion disorder. We demonstrate that necdin and Magel2 bind to and prevent proteasomal degradation of Fez1, a fasciculation and elongation protein implicated in axonal outgrowth and kinesin-mediated transport, and also bind to the Bardet-Biedl syndrome (BBS) protein BBS4 in co-transfected cells. The interactions among necdin, Magel2, Fez1 and BBS4 occur at or near centrosomes. Centrosomal or pericentriolar dysfunction has previously been implicated in BBS and may also be important in the features of PWS that overlap with BBS, such as learning disabilities, hypogonadism and obesity. Morphological abnormalities in axonal outgrowth and fasciculation manifest in several regions of the nervous system in necdin null mouse embryos, including axons of sympathetic, retinal ganglion cell, serotonergic and catecholaminergic neurons. These data demonstrate that necdin mediates intracellular processes essential for neurite outgrowth and that loss of necdin impinges on axonal outgrowth. We further suggest that loss of necdin contributes to the neurological phenotype of PWS, and raise the possibility that co-deletion of necdin and the related protein Magel2 may explain the lack of single gene mutations in PWS.

UR - http://www.scopus.com/inward/record.url?scp=14644391578&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=14644391578&partnerID=8YFLogxK

U2 - 10.1093/hmg/ddi059

DO - 10.1093/hmg/ddi059

M3 - Article

C2 - 15649943

AN - SCOPUS:14644391578

VL - 14

SP - 627

EP - 637

JO - Human Molecular Genetics

JF - Human Molecular Genetics

SN - 0964-6906

IS - 5

ER -