Tropomyosin Tpm3.1 Is Required to Maintain the Structure and Function of the Axon Initial Segment

被引：20
作者：
Abouelezz, Amr [1 ,2 ]
Stefen, Holly [3 ]
Segerstrale, Mikael [4 ]
Micinski, David [1 ]
Minkeviciene, Rimante [1 ]
Lahti, Lauri [5 ]
Hardeman, Edna C. [3 ]
Gunning, Peter W. [3 ]
Hoogenraad, Casper C. [6 ]
Taira, Tomi [7 ]
Fath, Thomas [3 ,8 ]
Hotulainen, Pirta [1 ]
机构：
[1] Minerva Fdn, Biomedicum Helsinki 2U, Tukholmankatu 8, Helsinki 00290, Finland
[2] Univ Helsinki, HiLIFE Neurosci Ctr, Haartmaninkatu 8, Helsinki 00290, Finland
[3] UNSW Sydney, Sch Med Sci, Sydney, NSW 2052, Australia
[4] Univ Helsinki, Fac Biol & Environm Sci, Viikinkaari 1, Helsinki 00790, Finland
[5] Aalto Univ, Sch Sci, Dept Comp Sci, Espoo, Finland
[6] Univ Utrecht, Fac Sci, Dept Biol, Cell Biol, Padualaan 8, NL-3584 CH Utrecht, Netherlands
[7] Univ Helsinki, Fac Vet Med, Agnes Sjobergin Katu 2, Helsinki 00790, Finland
[8] Macquarie Univ, Fac Med & Hlth Sci, Dementia Res Ctr, Sydney, NSW 2109, Australia
来源：
ISCIENCE | 2020年 / 23卷 / 05期
基金：
芬兰科学院; 英国医学研究理事会; 澳大利亚研究理事会;
关键词：
POLARIZED CARGO TRANSPORT; MYOSIN-II ACTIVITY; ANKYRIN-G; ACTIN CYTOSKELETON; MOLECULAR COMPOSITION; MEMBRANE SKELETON; BINDING PROTEINS; ISOFORMS; SPECTRIN; MAINTENANCE;
D O I：
10.1016/j.isci.2020.101053
中图分类号：
O [数理科学和化学]; P [天文学、地球科学]; Q [生物科学]; N [自然科学总论];
学科分类号：
07 ; 0710 ; 09 ;
摘要：
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.
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页数：50
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