TY - JOUR
T1 - Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment
AU - Abouelezz, Amr
AU - Stefen, Holly
AU - Segerstråle, Mikael
AU - Micinski, David
AU - Minkeviciene, Rimante
AU - Lahti, Lauri
AU - Hardeman, Edna C.
AU - Gunning, Peter W.
AU - Hoogenraad, Casper C.
AU - Taira, Tomi
AU - Fath, Thomas
AU - Hotulainen, Pirta
PY - 2020/5/22
Y1 - 2020/5/22
N2 - The axon initial segment (AIS) is the site of action potential initiation and serves as a cargo transport filter and diffusion barrier that helps maintain neuronal polarity. The AIS actin cytoskeleton comprises actin patches and periodic sub-membranous actin rings. We demonstrate that tropomyosin isoform Tpm3.1 co-localizes with actin patches and that the inhibition of Tpm3.1 led to a reduction in the density of actin patches. Furthermore, Tpm3.1 showed a periodic distribution similar to sub-membranous actin rings but Tpm3.1 was only partially congruent with sub-membranous actin rings. Nevertheless, the inhibition of Tpm3.1 affected the uniformity of the periodicity of actin rings. Furthermore, Tpm3.1 inhibition led to reduced accumulation of AIS structural and functional proteins, disruption in sorting somatodendritic and axonal proteins, and a reduction in firing frequency. These results show that Tpm3.1 is necessary for the structural and functional maintenance of the AIS.
AB - The axon initial segment (AIS) is the site of action potential initiation and serves as a cargo transport filter and diffusion barrier that helps maintain neuronal polarity. The AIS actin cytoskeleton comprises actin patches and periodic sub-membranous actin rings. We demonstrate that tropomyosin isoform Tpm3.1 co-localizes with actin patches and that the inhibition of Tpm3.1 led to a reduction in the density of actin patches. Furthermore, Tpm3.1 showed a periodic distribution similar to sub-membranous actin rings but Tpm3.1 was only partially congruent with sub-membranous actin rings. Nevertheless, the inhibition of Tpm3.1 affected the uniformity of the periodicity of actin rings. Furthermore, Tpm3.1 inhibition led to reduced accumulation of AIS structural and functional proteins, disruption in sorting somatodendritic and axonal proteins, and a reduction in firing frequency. These results show that Tpm3.1 is necessary for the structural and functional maintenance of the AIS.
KW - Biological Sciences
KW - Cell Biology
KW - Cellular Neuroscience
KW - Molecular Neuroscience
UR - http://www.scopus.com/inward/record.url?scp=85083547026&partnerID=8YFLogxK
U2 - 10.1016/j.isci.2020.101053
DO - 10.1016/j.isci.2020.101053
M3 - Article
AN - SCOPUS:85083547026
SN - 2589-0042
VL - 23
JO - iScience
JF - iScience
IS - 5
M1 - 101053
ER -