Myoblast fusion is essential for the formation of skeletal muscle myofibres. Studies have shown that phosphatidylserine is necessary for myoblast fusion, but the underlying mechanism is not known. Here we show that the phosphatidylserine receptor stabilin-2 acts as a membrane protein for myoblast fusion during myogenic differentiation and muscle regeneration. Stabilin-2 expression is induced during myogenic differentiation, and is regulated by calcineurin/NFAT signalling in myoblasts. Forced expression of stabilin-2 in myoblasts is associated with increased myotube formation, whereas deficiency of stabilin-2 results in the formation of small, thin myotubes. Stab2-deficient mice have myofibres with small cross-sectional area and few myonuclei and impaired muscle regeneration after injury. Importantly, myoblasts lacking stabilin-2 have reduced phosphatidylserine-dependent fusion. Collectively, our results show that stabilin-2 contributes to phosphatidylserine-dependent myoblast fusion and provide new insights into the molecular mechanism by which phosphatidylserine mediates myoblast fusion during muscle growth and regeneration.

Edited by Jesus AvilaKeywords: MEGF10 Amyloid-b Endocytosis Lipid raft pathway Alzheimer's disease a b s t r a c t MEGF10 is predominantly expressed in the brain and known to function as a phagocytic receptor. Here, we provide evidence that MEGF10 is involved in the uptake of amyloid-b peptide (Ab42) in the brain. Overexpression of MEGF10 dramatically increased Ab42 uptake in Hela cells. Knockdown of endogenous MEGF10 expression significantly decreased Ab42 uptake in N2A neuroblastoma cells. MEGF10-mediated Ab uptake is mostly dependent on lipid raft endocytosis pathway. Furthermore, site-directed mutagenesis revealed that the conserved cytoplasmic NPxY and YxxØ motifs are crucial for MEGF10-mediated uptake of Ab42 peptide. Thus, the identification of the MEGF10 as a functional receptor that mediates the uptake of amyloid-b peptide will help elucidate the molecular mechanisms of amlyoid-b clearance in Alzheimer's disease. Structured summary:MINT-7993537: ctxB (uniprotkb:P01556) and Abeta (uniprotkb:P05067) colocalize (MI:0403) by fluorescence microscopy (MI:0416) Ó

No abstract

No abstract