Journal article
The Stathmin-2 membrane targeting domain is required for axon protection and regulated degradation by DLK signaling
The Journal of biological chemistry, Vol.299(7), 104861
07/2023
DOI: 10.1016/j.jbc.2023.104861
PMCID: PMC10404615
PMID: 37236359
Abstract
Axon integrity is essential for functional connectivity in the nervous system. The degeneration of stressed or damaged axons is a common and sometimes initiating event in neurodegenerative disorders. Stathmin-2 (Stmn2) is an axon maintenance factor that is depleted in Amyotrophic Lateral Sclerosis, and replenishment of Stmn2 can restore neurite outgrowth in diseased neurons. However, mechanisms responsible for Stmn2-mediated axon maintenance in injured neurons are not known. We used primary sensory neurons to interrogate the role of Stmn2 in the degeneration of severed axons. We discover that membrane association of Stmn2 is critical for its axon-protective activity. Structure-function studies revealed that axonal enrichment of Stmn2 is driven by palmitoylation as well as tubulin interaction. Using live-imaging, we discover that another Stathmin, Stmn3, co-migrates with Stmn2-containing vesicles. We also demonstrate that Stmn3 undergoes regulated degradation through DLK-JNK signaling. The Stmn2 membrane targeting domain is both necessary and sufficient for localization to a specific vesicle population and confers sensitivity to DLK-dependent degradation. Our findings reveal a broader role for DLK in tuning the local abundance of palmitoylated Stathmins in axon segments. Moreover, palmitoylation is a critical component of Stathmin-mediated axon protection, and defining the Stmn2-containing vesicle population will provide important clues toward mechanisms of axon maintenance.
Details
- Title: Subtitle
- The Stathmin-2 membrane targeting domain is required for axon protection and regulated degradation by DLK signaling
- Creators
- Emma J.C. Thornburg-Suresh - Interdisciplinary Graduate Program in Neuroscience, , University of Iowa, Iowa City, IA 52242 USAJerianne E. Richardson - Department of Biology, University of Iowa, Iowa City, IA 52242 USADaniel W. Summers - Department of Biology, University of Iowa, Iowa City, IA 52242 USA
- Resource Type
- Journal article
- Publication Details
- The Journal of biological chemistry, Vol.299(7), 104861
- DOI
- 10.1016/j.jbc.2023.104861
- PMID
- 37236359
- PMCID
- PMC10404615
- NLM abbreviation
- J Biol Chem
- ISSN
- 0021-9258
- eISSN
- 1083-351X
- Publisher
- Elsevier Inc
- Grant note
- DOI: 10.13039/100000002, name: National Institutes of Health, award: RO1NS126191
- Language
- English
- Electronic publication date
- 05/24/2023
- Date published
- 07/2023
- Academic Unit
- Iowa Neuroscience Institute; Biology
- Record Identifier
- 9984421698502771
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