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

ABSTRACT: 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 appear at spermiogenesis step 9 in Actl7b-/- mice, finally resulting in spermatogenic arrest. Abnormal spermatids, were degraded. Co-immunoprecipitation experiments 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 are directly related to male infertility, pressing for additional research in men.

INSTRUMENT(S): Orbitrap Fusion Lumos

ORGANISM(S): Mus Musculus (mouse)

TISSUE(S): Testis, Sperm

DISEASE(S): Infertility

SUBMITTER: Marc Sylvester

LAB HEAD: Prof. Dr. Hubert Schorle

PROVIDER: PXD038920 | Pride | 2023-10-19

REPOSITORIES: Pride

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			Action	DRS
	220809_P-431-LA_194-199_Pool2_220828.mzML	Mzml
	220809_P-431-LA_194-199_Pool2_220828.mzid.gz	Mzid
	220809_P-431-LA_194-199_Pool2_220828.pdResult	Other
	220809_P-431-LA_194-199_Pool2_220828.pdResultView	Other
	220809_P-431-LA_195.raw	Raw

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