TY - JOUR
T1 - Ataxin-2 is essential for cytoskeletal dynamics and neurodevelopment in Drosophila
AU - del Castillo, Urko
AU - Norkett, Rosalind
AU - Lu, Wen
AU - Serpinskaya, Anna
AU - Gelfand, Vladimir I.
N1 - Funding Information:
We thank members of the Gelfand lab and Dr. M. Gelfand for helpful discussion. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. We thank Drs. A. Lim, W. Saxton and S. Rogers for Drosophila lines. This work was supported by the Northwestern University NUSeq Core Facility. Research reported in this study was supported by National Institute of General Medical Sciences Grants R01GM052111 and R35GM131752 (to V.I.G.).
Funding Information:
We thank members of the Gelfand lab and Dr. M. Gelfand for helpful discussion. Stocks obtained from the Bloomington Drosophila Stock Center (NIH P40OD018537) were used in this study. We thank Drs. A. Lim, W. Saxton and S. Rogers for Drosophila lines. This work was supported by the Northwestern University NUSeq Core Facility. Research reported in this study was supported by National Institute of General Medical Sciences Grants R01GM052111 and R35GM131752 (to V.I.G.). Conceptualization, UdC, RN and VG; Methodology, UdC, RN; Formal Analysis, UdC, RN; Investigation, UdC, RN, AS, WL; Writing original draft, RN; Writing ? review and editing, UdC, RN, VIG; Visualization, UdC, RN; Supervision, VIG; Funding Acquisition, VIG. The authors have nothing to disclose.
Publisher Copyright:
© 2021 The Author(s)
PY - 2022/1/21
Y1 - 2022/1/21
N2 - Ataxin-2 (Atx2) is a highly conserved RNA binding protein. Atx2 undergoes polyglutamine expansion leading to amyotrophic lateral sclerosis (ALS) or spinocerebellar ataxia type 2 (SCA2). However, the physiological functions of Atx2 in neurons remain unknown. Here, using the powerful genetics of Drosophila, we show that Atx2 is essential for normal neuronal cytoskeletal dynamics and organelle trafficking. Upon neuron-specific Atx2 loss, the microtubule and actin networks were abnormally stabilized and cargo transport was drastically inhibited. Depletion of Atx2 caused multiple morphological defects in the nervous system of third instar larvae. These include reduced brain size, impaired axon development, and decreased dendrite outgrowth. Defects in the nervous system caused loss of the ability to crawl and lethality at the pupal stage. Taken together, these data mark Atx2 as a major regulator of cytoskeletal dynamics and denote Atx2 as an essential gene in neurodevelopment, as well as a neurodegenerative factor.
AB - Ataxin-2 (Atx2) is a highly conserved RNA binding protein. Atx2 undergoes polyglutamine expansion leading to amyotrophic lateral sclerosis (ALS) or spinocerebellar ataxia type 2 (SCA2). However, the physiological functions of Atx2 in neurons remain unknown. Here, using the powerful genetics of Drosophila, we show that Atx2 is essential for normal neuronal cytoskeletal dynamics and organelle trafficking. Upon neuron-specific Atx2 loss, the microtubule and actin networks were abnormally stabilized and cargo transport was drastically inhibited. Depletion of Atx2 caused multiple morphological defects in the nervous system of third instar larvae. These include reduced brain size, impaired axon development, and decreased dendrite outgrowth. Defects in the nervous system caused loss of the ability to crawl and lethality at the pupal stage. Taken together, these data mark Atx2 as a major regulator of cytoskeletal dynamics and denote Atx2 as an essential gene in neurodevelopment, as well as a neurodegenerative factor.
KW - Biological sciences
KW - Cell biology
KW - Cellular neuroscience
KW - Developmental biology
KW - Developmental neuroscience
KW - Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85121264362&partnerID=8YFLogxK
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U2 - 10.1016/j.isci.2021.103536
DO - 10.1016/j.isci.2021.103536
M3 - Article
AN - SCOPUS:85121264362
VL - 25
JO - iScience
JF - iScience
SN - 2589-0042
IS - 1
M1 - 103536
ER -