Abstract
BackgroundLINC complexes are nuclear envelope bridging protein structures formed by interaction of SUN and KASH proteins. They physically connect the nucleus with the peripheral cytoskeleton and are critically involved in a variety of dynamic processes, such as nuclear anchorage, movement and positioning and meiotic chromosome dynamics. Moreover, they are shown to be essential for maintaining nuclear shape.FindingsBased on detailed expression analysis and biochemical approaches, we show here that during mouse sperm development, a terminal cell differentiation process characterized by profound morphogenic restructuring, two novel distinctive LINC complexes are established. They consist either of spermiogenesis-specific Sun3 and Nesprin1 or Sun1η, a novel non-nuclear Sun1 isoform, and Nesprin3. We could find that these two LINC complexes specifically polarize to opposite spermatid poles likely linking to sperm-specific cytoskeletal structures. Although, as shown in co-transfection/immunoprecipitation experiments, SUN proteins appear to arbitrarily interact with various KASH partners, our study demonstrates that they actually are able to confine their binding to form distinct LINC complexes.ConclusionsFormation of the mammalian sperm head involves assembly and different polarization of two novel spermiogenesis-specific LINC complexes. Together, our findings suggest that theses LINC complexes connect the differentiating spermatid nucleus to surrounding cytoskeletal structures to enable its well-directed shaping and elongation, which in turn is a critical parameter for male fertility.
Highlights
Anchorage and active positioning of the nucleus plays a fundamental role during diverse developmental processes such as fertilization, cell migration, establishment of polarity and is critical for differentiation of various cell types [1,2,3]
Our findings suggest that theses LINC complexes connect the differentiating spermatid nucleus to surrounding cytoskeletal structures to enable its well-directed shaping and elongation, which in turn is a critical parameter for male fertility
SUN proteins are integral inner nuclear membrane proteins with an N-terminal nucleoplasmic region separated by a TM domain from the Cterminal part that extends into the perinuclear space (PNS) [8,9]
Summary
Anchorage and active positioning of the nucleus plays a fundamental role during diverse developmental processes such as fertilization, cell migration, establishment of polarity and is critical for differentiation of various cell types [1,2,3] It essentially requires a direct interaction between the nucleus, in particular the nuclear envelope (NE), and the cytoskeleton. LINC complexes are nuclear envelope bridging protein structures formed by interaction of SUN and KASH proteins. They physically connect the nucleus with the peripheral cytoskeleton and are critically involved in a variety of dynamic processes, such as nuclear anchorage, movement and positioning and meiotic chromosome dynamics. They are shown to be essential for maintaining nuclear shape
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