Retrolinkin recruits the WAVE1 protein complex to facilitate BDNF-induced TrkB endocytosis and dendrite outgrowth
Open accessAbstract
Retrolinkin, a neuronal membrane protein, coordinates with endophilin A1 and mediates early endocytic trafficking and signal transduction of the ligand–receptor complex formed between brain-derived neurotrophic factor (BDNF) and its receptor, tropomyosin-related kinase B (TrkB), in dendrites of CNS neurons. Here we report that retrolinkin interacts with the CYFIP1/2 subunit of the WAVE1 complex, a member of the WASP/WAVE family of nucleation-promoting factors that binds and activates the Arp2/3 complex to promote branched actin polymerization. WAVE1, not N-WASP, is required for BDNF-induced TrkB endocytosis and dendrite outgrowth. Disruption of the interaction between retrolinkin and CYFIP1/2 impairs recruitment of WAVE1 to neuronal plasma membrane upon BDNF addition and blocks internalization of activated TrkB. We also show that WAVE1-mediated endocytosis of BDNF-activated TrkB is actin dependent and clathrin independent. These results not only reveal the mechanistic role of retrolinkin in BDNF–TrkB endocytosis, but also indicate that WASP/WAVE-dependent actin polymerization during endocytosis is regulated by cell type–specific and cargo-specific modulators.
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Retrolinkin interacts with CYFIP2 in the WAVE1 complex and facilitates BDNF-induced TRKB endocytosis and axonal outgrowth.
“Retrolinkin interacts with CYFIP2 in the WAVE1 complex and facilitates BDNF-induced TRKB endocytosis and axonal outgrowth58.”
From The WAVE complex in developmental and adulthood brain disorders (2025) · cites this paper as [58]
The Discussion reports that retrolinkin binds CYFIP1/2 in the WAVE1 complex and facilitates BDNF-induced TrkB endocytosis. It reports BDNF-induced dendrite outgrowth, not axonal outgrowth; that part of the claim is unsupported. (LLM, conf=0.90)
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Merrifield, C. J., Perrais, D., & Zenisek, D. (2005) · Cell · doi:10.1016/j.cell.2005.03.015 · Cited by 476 · cited 3× · see citing works
“…and kept increasing during the time monitored (Figure 5B), in agreement with the dynamics of both clathrin-dependent and -independent endocytosis (Merrifield et al., 2005; Mettlen et al., 2009; Basquin et al., 2015), colocalization between WAVE1 and ligand-activated TrkB (pTrk) in hippocampal…”
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Davenport, E. C., Szulc, B. R., Drew, J., Taylor, J., Morgan, T., Higgs, N. F., López-Doménech, G., & Kittler, J. T. (2019) · Cell Reports · doi:10.1016/j.celrep.2019.01.092 · Cited by 125 · see citing works
The WAVE complex in developmental and adulthood brain disorders
Kim, H.-G., Berdasco, C., Nairn, A. C., & Kim, Y. (2025) · Experimental & Molecular Medicine · doi:10.1038/s12276-024-01386-w · Cited by 8 · see citing works
- Authors
- Xu, C., Fu, X., Zhu, S., & Liu, J.-J.
- Affiliations
- Chinese Academy of Sciences (CN)
- Corresponding author
- Liu, Jia-Jia
- Venue
- Molecular Biology of the Cell
- Published
- 2016-11
- Volume
- 27
- Issue
- 21
- Pages
- 3342-3356
- ISSN
- 1059-1524 (ISSN-L)
- 1939-4586
- PMC
- PMC5170866
- OpenAlex
- W2515149348
- Cited by
- 27
- References
- 1
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 3 · 2023: 4 · 2022: 6 · 2021: 3 · 2020: 1 · 2019: 3 · 2018: 2 · 2017: 2
- FWCI
- 1.60
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Licence
- cc-by-nc-sa
- Locations
- Molecular Biology of the Cell (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-sa)
- PubMed Central (publishedVersion, cc-by-nc-sa)
- PubMed (publishedVersion)
- Funders
- National Natural Science Foundation of China
- Ministry of Science and Technology of the People's Republic of China
- University of Science and Technology of China
- Institute of Biophysics, Chinese Academy of Sciences
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Keywords
- WAVE1, BDNF signaling, dendritic outgrowth, Arp2/3 complex, actin polymerization, clathrin-independent endocytosis, endophilin A1
- MeSH terms
- Actins, Animals, Clathrin, Dendrites, Endocytosis, Membrane Proteins, Nerve Tissue Proteins, Neurons, Signal Transduction, Brain-Derived Neurotrophic Factor, Receptor, trkB, Protein Transport, Vesicular Transport Proteins, Adaptor Proteins, Signal Transducing, Wiskott-Aldrich Syndrome Protein Family, Actin-Related Protein 2-3 Complex, Mice
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