ICA1L forms BAR-domain complexes with PICK1 and is crucial for acrosome formation in spermiogenesis

J Cell Sci. 2015 Oct 15;128(20):3822-36. doi: 10.1242/jcs.173534. Epub 2015 Aug 25.


Mutations in the Pick1 gene cause globozoospermia, a male infertility disorder, in both mice and humans. PICK1 is crucial for vesicle trafficking, and its deficiency in sperm cells leads to abnormal vesicle trafficking from the Golgi to the acrosome. This eventually disrupts acrosome formation and leads to male infertility. Here, we identified ICA1L, which has sequence similarities to ICA69 (also known as ICA1), as a new BAR-domain binding partner of PICK1. ICA1L is expressed in testes and brain, and is the major binding partner for PICK1 in testes. ICA1L and PICK1 are highly expressed in spermatids and trafficked together at different stages of spermiogenesis. ICA1L-knockout mice were generated by CRISPR-Cas technology. PICK1 expression was reduced by 80% in the testes of male mice lacking ICA1L. Sperm from ICA1L-knockout mice had abnormalities in the acrosome, nucleus and mitochondrial sheath formation. Both total and mobile sperm numbers were reduced, and about half of the remaining sperm had the characteristics of globozoospermia. These defects ultimately resulted in reduced fertility of male ICA1L-knockout mice, and ICA69/ICA1L-double knockout male mice were sterile.

Keywords: Acrosome; Globozoospermia; ICA1L; Infertility; PICK1; Vesicle traffic.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acrosome / metabolism*
  • Animals
  • Autoantigens / genetics
  • Autoantigens / metabolism*
  • Carrier Proteins / genetics
  • Carrier Proteins / metabolism*
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Infertility, Male / genetics
  • Infertility, Male / metabolism
  • Male
  • Mice
  • Mice, Knockout
  • Nuclear Proteins / genetics
  • Nuclear Proteins / metabolism*
  • Rats
  • Spermatogenesis / physiology*


  • Autoantigens
  • Carrier Proteins
  • Cell Cycle Proteins
  • Cytoskeletal Proteins
  • Ica1 protein, mouse
  • Ica1 protein, rat
  • Nuclear Proteins
  • PICK1 protein, rat
  • Prkcabp protein, mouse