ApoD-SUN1 loop impairs young-cell polarity in mice

Daily intravenous injections of apolipoprotein D (ApoD) for ten days impaired muscle recovery after injury in mice: injured muscles had lower mass and contractile force than in control animals. Uninjured muscles were unaffected. That is the central in vivo finding from a bioRxiv preprint posted September 10.

The mechanism: old fibroblasts (connective tissue cells) secrete ApoD, which raises SUN1 levels in the inner nuclear membrane of young cells. SUN1 and nesprin-2 (a transmembrane protein) connect the nucleus to microtubules (protein filaments inside the cell). When SUN1 is elevated, that connection keeps the nucleus from reaching its correct position and disrupts cell polarity: the cell's ability to establish a front and rear for directed movement. The loop closes: high SUN1 itself drives further ApoD production and secretion. Suppressing SUN1 or severing the nucleus-to-microtubule link eliminated the polarity defect.

ApoD also raised SUN1 in muscle progenitor cells (the cells that give rise to muscle fibers) and impaired their ability to form fibers in culture. These cells directly participate in muscle regeneration, so the same mechanism explains the impaired recovery in mice that received ApoD.

This is an unreviewed preprint, and the work is in mice. The mechanism is specific and a molecular target (SUN1) is named, but the path from target to therapy is not addressed by the authors.

Experiment, a crowdfunding platform for scientific projects including cellular aging research, is in our database.

Open the related Eternal Search page

Sources
[1] biorxiv.org