| First Author | Merges GE | Year | 2023 |
| Journal | Development | Volume | 150 |
| Issue | 21 | PubMed ID | 37800308 |
| Mgi Jnum | J:342836 | Mgi Id | MGI:7548937 |
| Doi | 10.1242/dev.201593 | Citation | Merges GE, et al. (2023) Actl7b deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis. Development 150(21) |
| abstractText | Actin-related proteins (Arps) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp, and is highly conserved in rodents and primates. ACTL7B is specifically expressed in round and elongating spermatids during spermiogenesis. Here, we have generated an Actl7b-null allele in mice to unravel the role of ACTL7B in sperm formation. Male mice homozygous for the Actl7b-null allele (Actl7b-/-) were infertile, whereas heterozygous males (Actl7b+/-) were fertile. Severe spermatid defects, such as detached acrosomes, disrupted membranes and flagella malformations start to appear after spermiogenesis step 9 in Actl7b-/- mice, finally resulting in spermatogenic arrest. Abnormal spermatids were degraded and levels of autophagy markers were increased. Co-immunoprecipitation with mass spectrometry experiments identified an interaction between ACTL7B and the LC8 dynein light chains DYNLL1 and DYNLL2, which are first detected in step 9 spermatids and mislocalized when ACTL7B is absent. Our data unequivocally establish that mutations in ACTL7B are directly related to male infertility, pressing for additional research in humans. |
