| First Author | Alexander CJ | Year | 2021 |
| Journal | FASEB J | Volume | 35 |
| Issue | 1 | Pages | e21092 |
| PubMed ID | 33378124 | Mgi Jnum | J:308863 |
| Mgi Id | MGI:6741274 | Doi | 10.1096/fj.202001449R |
| Citation | Alexander CJ, et al. (2021) Myosin 18Aalpha targets the guanine nucleotide exchange factor beta-Pix to the dendritic spines of cerebellar Purkinje neurons and promotes spine maturation. FASEB J 35(1):e21092 |
| abstractText | Myosin 18Aalpha is a myosin 2-like protein containing unique N- and C-terminal protein interaction domains that co-assembles with myosin 2. One protein known to bind to myosin 18Aalpha is beta-Pix, a guanine nucleotide exchange factor (GEF) for Rac1 and Cdc42 that has been shown to promote dendritic spine maturation by activating the assembly of actin and myosin filaments in spines. Here, we show that myosin 18A concentrates in the spines of cerebellar Purkinje neurons via co-assembly with myosin 2 and through an actin binding site in its N-terminal extension. miRNA-mediated knockdown of myosin 18A results in a significant defect in spine maturation that is rescued by an RNAi-immune version of myosin 18A. Importantly, beta-Pix co-localizes with myosin 18A in spines, and its spine localization is lost upon myosin 18A knockdown or when its myosin 18A binding site is deleted. Finally, we show that the spines of myosin 18A knockdown Purkinje neurons contain significantly less F-actin and myosin 2. Together, these data argue that mixed filaments of myosin 2 and myosin 18A form a complex with beta-Pix in Purkinje neuron spines that promotes spine maturation by enhancing the assembly of actin and myosin filaments downstream of beta-Pix's GEF activity. |
