QNQKE targeting motif for the SMN-Gemin multiprotein complexin neurons.
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.
Zhang
Honglai
H
Department of Anatomy and Structural Biology, Albert Einstein College of Medicine, Bronx, New York, USA.
Xing
Lei
L
Singer
Robert H
RH
Bassell
Gary J
GJ
D000595:Amino Acid Sequence / Q000502:physiology*; D000818:Animals; D002478:Cells, Cultured; D002642:Chick Embryo; D002522:Chlorocebus aethiops; D017362:Cyclic AMP Response Element-Binding Protein / Q000737:chemistry* / Q000378:metabolism*; D006801:Humans; D008164:Luminescent Proteins / Q000378:metabolism; D009154:Mutation / Q000502:physiology; D009419:Nerve Tissue Proteins / Q000737:chemistry* / Q000378:metabolism*; D009474:Neurons / Q000166:cytology / Q000378:metabolism*; D016548:Prosencephalon / Q000166:cytology; D021381:Protein Transport / Q000502:physiology*; D016601:RNA-Binding Proteins / Q000737:chemistry* / Q000378:metabolism*; D012261:Ribonucleoproteins / Q000378:metabolism; D055532:SMN Complex Proteins; D014162:Transfection / Q000379:methods
D017362:Cyclic AMP Response Element-Binding Protein; D008164:Luminescent Proteins; D009419:Nerve Tissue Proteins; D016601:RNA-Binding Proteins; D012261:Ribonucleoproteins; D055532:SMN Complex Proteins; C026452:messenger ribonucleoprotein