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UNC5B is an isoform-dependent target for ectodomain shedding
Kotaro Sugimoto1, Eichi Watabe2,3, Mio Takuma1
1Department of Biomedical Sciences, College of Life Sciences, Ritsumeikan University, 1-1-1 Nojihigashi, Kusatsu, Shiga 525-8577, Japan.
Journal of Biochemistry
|July 9, 2025
Summary
Ectodomain shedding, a protein processing event, is influenced by alternative splicing. This study reveals that skipping specific exons alters the shedding of UNC5B, a Netrin-1 receptor, impacting its biological roles.
Area of Science:
- Molecular Biology
- Cell Biology
- Neuroscience
Background:
- Ectodomain shedding is a post-translational modification regulating membrane protein function.
- The physiological roles of ectodomain shedding remain incompletely understood.
- Alternative splicing of juxtamembrane regions can affect protein shedding.
Purpose of the Study:
- To investigate the impact of alternative splicing on the ectodomain shedding of membrane proteins.
- To determine if exon skipping influences the shedding susceptibility of UNC5B, a Netrin-1 receptor.
Main Methods:
- Screening of membrane proteins for altered shedding susceptibility due to exon skipping.
- Analysis of UNC5B splice variants and their shedding characteristics.
Main Results:
- Identified that skipping or inclusion of specific exons encoding the juxtamembrane region alters UNC5B shedding.
- Demonstrated a splice isoform-dependent regulation of UNC5B shedding.
Conclusions:
- Alternative splicing of the juxtamembrane region is a mechanism to regulate UNC5B shedding.
- UNC5B shedding, modulated by splice isoforms, may play a role in neural circuit formation, angiogenesis, and cancer development.
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