Abstract
ABSTRACTMicrotubule actin crosslinking factor 1 (MACF1) is a widely expressed cytoskeletal linker and plays an essential role in various cells’ functions by mediating cytoskeleton organization and dynamics. However, the role of MACF1 on preosteoblast migration is not clear. Here, by using MACF1 knockdown and overexpressed MC3T3-E1 cells, we found MACF1 positively regulated preosteoblast migration induced by cell polarization. Furthermore, immunofluorescent staining showed that MACF1 increased end-binding protein (EB1) distribution on microtubule (MT), and decreased EB1 distribution on focal adhesion (FA) complex. Moreover, upregulation of MACF1 activated Src level and enhanced the colocalization of EB1 with activated Src. In addition, MACF1 diminished colocalization of EB1 with adenomatous polyposis coli (APC), which induced EB1 release from FA and promoted FA turnover. These results indicated an important role and mechanism of MACF1 in regulating preosteoblast migration through promoting FA turnover by mediating EB1 colocalization with Src and APC, which inferred that MACF1 might be a potential target for preventing and treating bone disorders.
Highlights
Preosteoblast or their precursors can migrate into bone resorption cavities and attach to the bottom of those cavities
For Microtubule actin crosslinking factor 1 (MACF1) knockdown MC3T3-E1, migratory cell numbers decreased by 64.3±4% (Fig. 1C), and cell migration distance was reduced by 37.5±0.9% (Fig. 1E, P
Most studies mainly focus on preosteoblast/osteoblast differentiation and proliferation to clarify pathogenesis of bone disorder
Summary
Preosteoblast or their precursors can migrate into bone resorption cavities and attach to the bottom of those cavities. These are critical events in maintaining bone mass (Dirckx et al, 2013; Shirakawa et al, 2014). Improving preosteoblast/precursor migration is a potential strategy for bone disease treatments, such as for osteoporosis and bone fractures (Su et al, 2018). Polarization is the critical event for cell migration. During polarization and directed motility in wound healing, Golgi become positioned towards the wound edge. The position of Golgi body relative to the nucleus is considered to be a sensitive indicator for cell polarization. The ratio of length/width is another indicator for cell polarization
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