Meiotic lamin C2: The unique amino-terminal hexapeptide GNAEGR is essential for nuclear envelope association

Meiotic lamin C2 is the only A-type lamin expressed during mammalian sperma togenesis. Typical for this short lamin is the unique hexapeptide GNAECR, w hich substitutes the nonhelical amino terminus and part of the alpha -helic al rod domain present in somatic lamins. Meiotic lamin C2 also lacks a carb oxyl-terminal CaaX box, which is modified by isoprenylation and involved in nuclear envelope (NE) association of somatic isoforms, The mechanism by wh ich lamin C2 becomes localized in the NE is totally unknown. Here we demons trate that the hexapeptide GNAECR is essential for this process: (i) Its de letion resulted in a diffuse distribution of lamin C2 within nuclei of tran sfected COS-7 cells; (ii) Mutated somatic lamin C, containing the sequence GNAEGR at its amino terminus, was located at the NE. The mass spectrometric analysis of the amino terminus of lamin C2 revealed that it is modified by myristoylation. Correspondingly, the substitution of the first glycine res idue abolishes the NE association of lamin C2, We conclude that NE associat ion of lamin C2 is achieved by a mechanism different from that of somatic l amins,