Filamin-A-interacting protein 1 (FILIP1) is a dual compartment protein linking myofibrils and microtubules during myogenic differentiation and upon mechanical stress.

Valentina Grande, Julia Schuld, Peter F M van der Ven, Oliver J Gruss, Dieter O Fürst

Cell and tissue research 2023 Jul

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Variations in the gene encoding filamin-A-interacting protein 1 (FILIP1) were identified to be associated with a combination of neurological and muscular symptoms. While FILIP1 was shown to regulate motility of brain ventricular zone cells, a process important for corticogenesis, the function of the protein in muscle cells has been less well characterized. The expression of FILIP1 in regenerating muscle fibres predicted a role in early muscle differentiation. Here we analysed expression and localization of FILIP1 and its binding partners filamin-C (FLNc) and microtubule plus-end-binding protein EB3 in differentiating cultured myotubes and adult skeletal muscle. Prior to the development of cross-striated myofibrils, FILIP1 is associated with microtubules and colocalizes with EB3. During further myofibril maturation its localization changes, and FILIP1 localizes to myofibrillar Z-discs together with the actin-binding protein FLNc. Forced contractions of myotubes by electrical pulse stimulation (EPS) induce focal disruptions in myofibrils and translocation of both proteins from Z-discs to these lesions, suggesting a role in induction and/or repair of these structures. The immediate proximity of tyrosylated, dynamic microtubules and EB3 to lesions implies that also these play a role in these processes. This implication is supported by the fact that in nocodazole-treated myotubes that lack functional microtubules, the number of lesions induced by EPS is significantly reduced. In summary, we here show that FILIP1 is a cytolinker protein that is associated with both microtubules and actin filaments, and might play a role in the assembly of myofibrils and their stabilization upon mechanical stress to protect them from damage. © 2023. The Author(s).

Citation

Valentina Grande, Julia Schuld, Peter F M van der Ven, Oliver J Gruss, Dieter O Fürst. Filamin-A-interacting protein 1 (FILIP1) is a dual compartment protein linking myofibrils and microtubules during myogenic differentiation and upon mechanical stress. Cell and tissue research. 2023 Jul;393(1):133-147