SUN5 forms a regular protein lattice reinforcing the sperm head-tail junction

Area of Science:

• Cell biology
• Structural biology
• Reproductive biology

Background:

• Spermatozoa require specific morphology for fertilization.
• Acephalic spermatozoa syndrome, causing infertility, results from sperm head-tail detachment.
• Mutations in SUN5, a linker of nucleo- and cytoskeleton (LINC) complex component, are a common genetic cause of this syndrome.

Purpose of the Study:

• To investigate the structural role of sperm-specific SUN5 in nuclear envelope organization.
• To elucidate the molecular mechanism underlying SUN5 function in sperm morphology.
• To provide a structural basis for SUN5 mutations causing infertility.

Main Methods:

• Superresolution fluorescence microscopy to determine SUN5 localization in human, mouse, and boar sperm.
• In situ cryoelectron tomography to analyze the ultrastructure of the sperm nuclear envelope.
• Structural analysis to model LINC complex interactions.

Main Results:

• Sperm-specific SUN5 localizes to the sperm head base.
• An extensive hexagonal lattice structure of the linker of nucleo- and cytoskeleton (LINC) complex was identified in the nuclear envelope at the sperm head base.
• This lattice maintains close apposition between inner and outer nuclear membranes, suggesting lateral interactions of LINC complexes at the outer nuclear membrane.

Conclusions:

• The linker of nucleo- and cytoskeleton (LINC) complex forms a hexagonal lattice at the sperm head base, organizing the nuclear envelope.
• This structure is crucial for maintaining sperm morphology and head-tail stability.
• Understanding this structure rationalizes the infertility caused by SUN5 mutations.