QNQKE targeting motif for the SMN-gemin multiprotein complex in neurons

Honglai Zhang, Lei Xing, Robert H. Singer, Gary J. Bassell

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Spinal muscular atrophy (SMA) is a heritable neurodegenerative disease affecting motor neurons that is caused by the impaired expression of the full-length form of the survival of motor neuron protein (SMN), which may have a specialized function in neurons related to mRNA localization. We have previously shown that a population SMN complexes contain Gemin ribonucleoproteins and traffic in the form of granules to neuronal processes and growth cones of cultured neurons. A QNQKE sequence within exon 7 has been shown to be necessary for both cytoplasmic localization of SMN and axonal function. Here we show that the QNQKE sequence can influence the nucleocytoplasmic distribution of the SMN-Gemin complex and its localization into neuronal processes. QNQKE exerted a stronger effect on SMN localization in primary neurons compared with COS-7 cells. By using double-label fluorescence in situ hybridization and immunofluorescence, SMN granules within neuronal processes colocalized with poly(A) mRNA and PABP. These findings provide further evidence in support of a neuronal function for SMN and motivation to investigate for impaired assembly and/or localization of mRNP complexes as an underlying cause of SMA.

Original languageEnglish (US)
Pages (from-to)2657-2667
Number of pages11
JournalJournal of Neuroscience Research
Volume85
Issue number12
DOIs
StatePublished - Sep 2007

Fingerprint

SMN Complex Proteins
Multiprotein Complexes
Motor Neurons
Neurons
Spinal Muscular Atrophy
Proteins
Growth Cones
Messenger RNA
Ribonucleoproteins
COS Cells
Fluorescence In Situ Hybridization
Neurodegenerative Diseases
Fluorescent Antibody Technique
Exons

Keywords

  • Motor neuron disease
  • mRNA localization
  • mRNA transport
  • Ribonucleoprotein (RNP)
  • Spinal muscular atrophy (SMA)
  • Survival of motor neuron protein (SMN)

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

QNQKE targeting motif for the SMN-gemin multiprotein complex in neurons. / Zhang, Honglai; Xing, Lei; Singer, Robert H.; Bassell, Gary J.

In: Journal of Neuroscience Research, Vol. 85, No. 12, 09.2007, p. 2657-2667.

Research output: Contribution to journalArticle

Zhang, Honglai ; Xing, Lei ; Singer, Robert H. ; Bassell, Gary J. / QNQKE targeting motif for the SMN-gemin multiprotein complex in neurons. In: Journal of Neuroscience Research. 2007 ; Vol. 85, No. 12. pp. 2657-2667.
@article{bd143677ec6d4593b5903afd0909d907,
title = "QNQKE targeting motif for the SMN-gemin multiprotein complex in neurons",
abstract = "Spinal muscular atrophy (SMA) is a heritable neurodegenerative disease affecting motor neurons that is caused by the impaired expression of the full-length form of the survival of motor neuron protein (SMN), which may have a specialized function in neurons related to mRNA localization. We have previously shown that a population SMN complexes contain Gemin ribonucleoproteins and traffic in the form of granules to neuronal processes and growth cones of cultured neurons. A QNQKE sequence within exon 7 has been shown to be necessary for both cytoplasmic localization of SMN and axonal function. Here we show that the QNQKE sequence can influence the nucleocytoplasmic distribution of the SMN-Gemin complex and its localization into neuronal processes. QNQKE exerted a stronger effect on SMN localization in primary neurons compared with COS-7 cells. By using double-label fluorescence in situ hybridization and immunofluorescence, SMN granules within neuronal processes colocalized with poly(A) mRNA and PABP. These findings provide further evidence in support of a neuronal function for SMN and motivation to investigate for impaired assembly and/or localization of mRNP complexes as an underlying cause of SMA.",
keywords = "Motor neuron disease, mRNA localization, mRNA transport, Ribonucleoprotein (RNP), Spinal muscular atrophy (SMA), Survival of motor neuron protein (SMN)",
author = "Honglai Zhang and Lei Xing and Singer, {Robert H.} and Bassell, {Gary J.}",
year = "2007",
month = "9",
doi = "10.1002/jnr.21308",
language = "English (US)",
volume = "85",
pages = "2657--2667",
journal = "Journal of Neuroscience Research",
issn = "0360-4012",
publisher = "Wiley-Liss Inc.",
number = "12",

}

TY - JOUR

T1 - QNQKE targeting motif for the SMN-gemin multiprotein complex in neurons

AU - Zhang, Honglai

AU - Xing, Lei

AU - Singer, Robert H.

AU - Bassell, Gary J.

PY - 2007/9

Y1 - 2007/9

N2 - Spinal muscular atrophy (SMA) is a heritable neurodegenerative disease affecting motor neurons that is caused by the impaired expression of the full-length form of the survival of motor neuron protein (SMN), which may have a specialized function in neurons related to mRNA localization. We have previously shown that a population SMN complexes contain Gemin ribonucleoproteins and traffic in the form of granules to neuronal processes and growth cones of cultured neurons. A QNQKE sequence within exon 7 has been shown to be necessary for both cytoplasmic localization of SMN and axonal function. Here we show that the QNQKE sequence can influence the nucleocytoplasmic distribution of the SMN-Gemin complex and its localization into neuronal processes. QNQKE exerted a stronger effect on SMN localization in primary neurons compared with COS-7 cells. By using double-label fluorescence in situ hybridization and immunofluorescence, SMN granules within neuronal processes colocalized with poly(A) mRNA and PABP. These findings provide further evidence in support of a neuronal function for SMN and motivation to investigate for impaired assembly and/or localization of mRNP complexes as an underlying cause of SMA.

AB - Spinal muscular atrophy (SMA) is a heritable neurodegenerative disease affecting motor neurons that is caused by the impaired expression of the full-length form of the survival of motor neuron protein (SMN), which may have a specialized function in neurons related to mRNA localization. We have previously shown that a population SMN complexes contain Gemin ribonucleoproteins and traffic in the form of granules to neuronal processes and growth cones of cultured neurons. A QNQKE sequence within exon 7 has been shown to be necessary for both cytoplasmic localization of SMN and axonal function. Here we show that the QNQKE sequence can influence the nucleocytoplasmic distribution of the SMN-Gemin complex and its localization into neuronal processes. QNQKE exerted a stronger effect on SMN localization in primary neurons compared with COS-7 cells. By using double-label fluorescence in situ hybridization and immunofluorescence, SMN granules within neuronal processes colocalized with poly(A) mRNA and PABP. These findings provide further evidence in support of a neuronal function for SMN and motivation to investigate for impaired assembly and/or localization of mRNP complexes as an underlying cause of SMA.

KW - Motor neuron disease

KW - mRNA localization

KW - mRNA transport

KW - Ribonucleoprotein (RNP)

KW - Spinal muscular atrophy (SMA)

KW - Survival of motor neuron protein (SMN)

UR - http://www.scopus.com/inward/record.url?scp=34548309100&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=34548309100&partnerID=8YFLogxK

U2 - 10.1002/jnr.21308

DO - 10.1002/jnr.21308

M3 - Article

C2 - 17455327

AN - SCOPUS:34548309100

VL - 85

SP - 2657

EP - 2667

JO - Journal of Neuroscience Research

JF - Journal of Neuroscience Research

SN - 0360-4012

IS - 12

ER -