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

Actin-related proteins (Arp) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp and highly conserved in rodents and primates. ACTL7B is specifically expressed in round and elongating spermatids during spermiogenesis....

Full description

Saved in:
Bibliographic Details
Published inbioRxiv
Main Authors Merges, Gina Esther, Arevalo, Lena, Lohanadan, Keerthika, De Rooij, Dirk G, Jokwitz, Melanie, Witke, Walter, Schorle, Hubert
Format Paper
LanguageEnglish
Published Cold Spring Harbor Cold Spring Harbor Laboratory Press 19.12.2022
Subjects
Acrosomes
Actin
Alleles
Dynein
Immunoprecipitation
Infertility
Light chains
Spermatids
Spermatogenesis
Spermiogenesis
Online AccessGet full text

Cover

More Information
Summary:Actin-related proteins (Arp) are classified according to their similarity to actin and are involved in diverse cellular processes. ACTL7B is a testis-specific Arp and 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, while heterozygous males (Actl7b+/-) were fertile. Severe spermatid defects such as detached acrosomes, disrupted membranes and failed elongation of the axoneme start to accumulate at step 9 in Actl7b-/- mice, finally resulting in spermatogenic arrest. Abnormal spermatids, became degraded. Co-immunoprecipitation identified 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 establishes that mutations in ACTL7B may be directly related to male infertility, pressing for additional research in men.Competing Interest StatementThe authors have declared no competing interest.
DOI:10.1101/2022.12.19.520998