Actl7b deficiency leads to mislocalization of LC8 type dynein light chains and disruption of murine spermatogenesis

• Published in: Development (Cambridge) Vol. 150; no. 21
• Main Authors: Merges, Gina E., Arévalo, Lena, Kovacevic, Andjela, Lohanadan, Keerthika, de Rooij, Dirk G., Simon, Carla, Jokwitz, Melanie, Witke, Walter, Schorle, Hubert
• Format: Journal Article
• Language: English
• Published: 01.11.2023
• ISSN: 0950-1991; 1477-9129
• DOI: 10.1242/dev.201593

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.