TY - JOUR
T1 - Nerve-independent formation of membrane infoldings at topologically complex postsynaptic apparatus by caveolin-3
AU - Kwan, Hui-Lam Rachel
AU - Chan, Zora Chui-Kuen
AU - Bi, Xinyi
AU - Kutkowska, Justyna
AU - Prószyński, Tomasz J.
AU - Chan, Chi Bun
AU - Lee, Chi Wai
N1 - Funding: This project was partly supported by the General Research Fund (17100718, 17100219, and 17111521) from Research Grants Council of Hong Kong to C.W.L. and National Science Center, Poland grant (Opus 2020/37/B/NZ3/03909) to T.J.P.
PY - 2023/6
Y1 - 2023/6
N2 - Junctional folds are unique membrane specializations developed progressively during the postnatal maturation of vertebrate neuromuscular junctions (NMJs), but how they are formed remains elusive. Previous studies suggested that topologically complex acetylcholine receptor (AChR) clusters in muscle cultures undergo a series of transformations, resembling the postnatal maturation of NMJs in vivo. We first demonstrated the presence of membrane infoldings at AChR clusters in cultured muscles. Live-cell super-resolution imaging further revealed that AChRs are gradually redistributed to the crest regions and spatially segregated from acetylcholinesterase along the elongating membrane infoldings over time. Mechanistically, lipid raft disruption or caveolin-3 knockdown not only inhibits membrane infolding formation at aneural AChR clusters and delays agrin-induced AChR clustering in vitro but also affects junctional fold development at NMJs in vivo. Collectively, this study demonstrated the progressive development of membrane infoldings via nerve-independent, caveolin-3–dependent mechanisms and identified their roles in AChR trafficking and redistribution during the structural maturation of NMJs.
AB - Junctional folds are unique membrane specializations developed progressively during the postnatal maturation of vertebrate neuromuscular junctions (NMJs), but how they are formed remains elusive. Previous studies suggested that topologically complex acetylcholine receptor (AChR) clusters in muscle cultures undergo a series of transformations, resembling the postnatal maturation of NMJs in vivo. We first demonstrated the presence of membrane infoldings at AChR clusters in cultured muscles. Live-cell super-resolution imaging further revealed that AChRs are gradually redistributed to the crest regions and spatially segregated from acetylcholinesterase along the elongating membrane infoldings over time. Mechanistically, lipid raft disruption or caveolin-3 knockdown not only inhibits membrane infolding formation at aneural AChR clusters and delays agrin-induced AChR clustering in vitro but also affects junctional fold development at NMJs in vivo. Collectively, this study demonstrated the progressive development of membrane infoldings via nerve-independent, caveolin-3–dependent mechanisms and identified their roles in AChR trafficking and redistribution during the structural maturation of NMJs.
UR - http://www.scopus.com/inward/record.url?scp=85163902714&partnerID=8YFLogxK
U2 - 10.1126/sciadv.adg0183
DO - 10.1126/sciadv.adg0183
M3 - Journal article
SN - 2375-2548
VL - 9
JO - Science Advances
JF - Science Advances
IS - 24
M1 - eadg0183
ER -