Abstract
Vertebrate nervous systems use the axon initial segment (AIS) to initiate action potentials and maintain neuronal polarity. The microtubule-associated protein tripartite motif containing 46 (TRIM46) was reported to regulate axon specification, AIS assembly, and neuronal polarity through the bundling, or fasciculation, of microtubules in the proximal axon. However, these claims are based on TRIM46 knockdown in cultured neurons. To investigate TRIM46 function in vivo, we examined male and female TRIM46 knock-out mice. Contrary to previous reports, we find that TRIM46 is dispensable for axon specification and AIS formation. TRIM46 knock-out mice are viable, have normal behavior, and have normal brain structure. Thus, TRIM46 is not required for AIS formation, axon specification, or nervous system function. However, we confirm that TRIM46 is required for microtubule fasciculation. We also show TRIM46 enrichment in the first ∼100 μm of axon occurs independently of ankyrinG (AnkG) in vivo, although AnkG is required to restrict TRIM46 only to the AIS. Our results highlight the need for further investigation of the mechanisms by which the AIS and microtubules interact to shape neuronal structure and function.
Original language | English |
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Article number | e0976242024 |
Journal | Journal of Neuroscience |
Volume | 44 |
Issue number | 42 |
DOIs | |
Publication status | Published - 16 Oct 2024 |
Funding
This work is supported by grants from the National Institutes of Health: R35 NS122073 (M.N.R.) and F31 NS134125 (A.J.M.), the Dr. Miriam and Sheldon G. Adelson Medical Research Foundation (M.N.R., A.L.B., and E.P.), and the US–Israel Binational Science Foundation (M.N.R. and E.P.). We thank Dr. Lindsay Teliska for the help with AnkG cKO mice and Dr. Xiaoyun Ding for the help with behavioral experiments. The TRIM46 transcript expression data in the pituitary gland mentioned in this manuscript was obtained from the GTEx Portal on 08/08/24. Publisher Copyright: Copyright © 2024 the authors.
All Science Journal Classification (ASJC) codes
- General Neuroscience