TY - JOUR
T1 - The COPI vesicle complex binds and moves with survival motor neuron within axons
AU - Peter, Cyril Jayakumar
AU - Evans, Matthew
AU - Thayanithy, Venugopal
AU - Taniguchi-Ishigaki, Naoko
AU - Bach, Ingolf
AU - Kolpak, Adrianne
AU - Bassell, Gary J.
AU - Rossoll, Wilfried
AU - Lorson, Christian L.
AU - Bao, Zheng Zheng
AU - Androphy, Elliot J.
N1 - Funding Information:
This work was supported in part by Muscular Dystrophy Association, USA grant #68695 to E.J.A. and NIH RO1HD055835 to G.J.B.
PY - 2011/5
Y1 - 2011/5
N2 - Spinal muscular atrophy (SMA), an inherited disease of motor neuron dysfunction, results from insufficient levels of the survival motor neuron (SMN) protein. Movement of the SMN protein as granules within cultured axons suggests that the pathogenesis of SMA may involve defects in neuronal transport, yet the nature of axon transport vesicles remains enigmatic. Here we show that SMN directly binds to the a-subunit of the coat protein I (COPI) vesicle coat protein. The α-COP protein co-immunoprecipitates with SMN, small nuclear ribonucleoprotein-associated assembly factors and β-actin mRNA. Although typically Golgi associated, in neuronal cells α-COP localizes to lamellipodia and growth cones and moves within the axon, with a subset of these granules traveling together with SMN. Depletion of α-COP resulted in mislocalization of SMN and actin at the leading edge at the lamellipodia. We propose that neurons utilize the Golgi-associated COPI vesicle to deliver cargoes necessary for motor neuron integrity and function.
AB - Spinal muscular atrophy (SMA), an inherited disease of motor neuron dysfunction, results from insufficient levels of the survival motor neuron (SMN) protein. Movement of the SMN protein as granules within cultured axons suggests that the pathogenesis of SMA may involve defects in neuronal transport, yet the nature of axon transport vesicles remains enigmatic. Here we show that SMN directly binds to the a-subunit of the coat protein I (COPI) vesicle coat protein. The α-COP protein co-immunoprecipitates with SMN, small nuclear ribonucleoprotein-associated assembly factors and β-actin mRNA. Although typically Golgi associated, in neuronal cells α-COP localizes to lamellipodia and growth cones and moves within the axon, with a subset of these granules traveling together with SMN. Depletion of α-COP resulted in mislocalization of SMN and actin at the leading edge at the lamellipodia. We propose that neurons utilize the Golgi-associated COPI vesicle to deliver cargoes necessary for motor neuron integrity and function.
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U2 - 10.1093/hmg/ddr046
DO - 10.1093/hmg/ddr046
M3 - Article
C2 - 21300694
AN - SCOPUS:79954519035
SN - 0964-6906
VL - 20
SP - 1701
EP - 1711
JO - Human molecular genetics
JF - Human molecular genetics
IS - 9
M1 - ddr046
ER -