A brain specific alternatively spliced isoform of nonmuscle myosin IIA lacks its mechano-enzymatic activities

• Published in: The Journal of biological chemistry 2023-08, p.105143
• Main Authors: Das, Samprita, Mallick, Ditipriya, Sarkar, Sourav, Billington, Neil, Sellers, James R, Jana, Siddhartha S
• Format: Article
• Language: English
• ISSN: 1083-351X
• DOI: 10.1016/j.jbc.2023.105143

Recent genomic studies reported 90-95% of human genes can undergo alternative splicing, by which multiple isoforms of proteins are synthesized. However, the functional consequences of most of the isoforms are largely unknown. Here, we report a novel alternatively spliced isoform of nonmuscle myosin IIA (NM IIA), called NM IIA2, which is generated by the inclusion of 21 amino acids near the actin binding region (loop 2) of the head domain of heavy chains. Expression of NM IIA2 is found exclusively in the brain tissue, where it reaches a maximum level at 24h during the circadian rhythm. The actin-dependent Mg -ATPase activity and in vitro motility assays reveal that NM IIA2 lacks its motor activities but localizes with actin filaments in cells. Interestingly, NM IIA2 can also make heterofilaments with NM IIA0 (non-inserted isoform of NM IIA) and can retard the in vitro motility of NM IIA, when the two are mixed. Altogether, our findings provide the functional importance of a previously unknown alternatively spliced isoform, NM IIA2, and its potential physiological role in regulating NM IIA activity in the brain.