TY - JOUR
T1 - A Drosophila melanogaster model of spinal muscular atrophy reveals a function for SMN in striated muscle
AU - Rajendra, T. K.
AU - Gonsalvez, Graydon B.
AU - Walker, Michael P.
AU - Shpargel, Karl B.
AU - Salz, Helen K.
AU - Matera, A. Gregory
PY - 2007/3/12
Y1 - 2007/3/12
N2 - 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.
AB - 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.
UR - http://www.scopus.com/inward/record.url?scp=33947217787&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33947217787&partnerID=8YFLogxK
U2 - 10.1083/jcb.200610053
DO - 10.1083/jcb.200610053
M3 - Article
C2 - 17353360
AN - SCOPUS:33947217787
SN - 0021-9525
VL - 176
SP - 831
EP - 841
JO - Journal of Cell Biology
JF - Journal of Cell Biology
IS - 6
ER -