A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle

T. K. Rajendra, Graydon Bennett Gonsalvez, Michael P. Walker, Karl B. Shpargel, Helen K. Salz, A. Gregory Matera

Research output: Contribution to journalArticle

112 Citations (Scopus)

Abstract

Mutations in human survival motor neurons 1 (SMN1) cause spinal muscular atrophy (SMA) and are associated with defects in assembly of small nuclear ribonucleoproteins (snRNPs) in vitro. However, the etiological link between snRNPs and SMA is unclear. We have developed a Drosophila melanogaster system to model SMA in vivo. Larval-lethal Smn-null mutations show no detectable snRNP reduction, making it unlikely that these animals die from global snRNP deprivation. Hypomorphic mutations in Smn reduce dSMN protein levels in the adult thorax, causing flightlessness and acute muscular atrophy. Mutant flight muscle motoneurons display pronounced axon routing and arborization defects. Moreover, Smn mutant myofibers fail to form thin filaments and phenocopy null mutations in Act88F, which is the flight muscle-specific actin isoform. In wildtype muscles, dSMN colocalizes with sarcomeric actin and forms a complex with ?-actinin, the thin filament crosslinker. The sarcomeric localization of Smn is conserved in mouse myofibrils. These observations suggest a muscle-specific function for SMN and underline the importance of this tissue in modulating SMA severity.

Original languageEnglish (US)
Pages (from-to)831-841
Number of pages11
JournalJournal of Cell Biology
Volume176
Issue number6
DOIs
StatePublished - Mar 12 2007
Externally publishedYes

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Small Nuclear Ribonucleoproteins
Spinal Muscular Atrophy
Striated Muscle
Drosophila melanogaster
Muscles
Mutation
Motor Neurons
Actins
Spinal Muscular Atrophies of Childhood
Actinin
Muscular Atrophy
Myofibrils
Axons
Protein Isoforms
Thorax
Proteins

ASJC Scopus subject areas

  • Cell Biology

Cite this

A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. / Rajendra, T. K.; Gonsalvez, Graydon Bennett; Walker, Michael P.; Shpargel, Karl B.; Salz, Helen K.; Matera, A. Gregory.

In: Journal of Cell Biology, Vol. 176, No. 6, 12.03.2007, p. 831-841.

Research output: Contribution to journalArticle

Rajendra, T. K. ; Gonsalvez, Graydon Bennett ; Walker, Michael P. ; Shpargel, Karl B. ; Salz, Helen K. ; Matera, A. Gregory. / A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle. In: Journal of Cell Biology. 2007 ; Vol. 176, No. 6. pp. 831-841.
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