Human 76p: A new member of the gamma-tubulin-associated protein family

The role of the centrosomes in microtubule nucleation remains largely unkno wn at the molecular level, gamma-Tubulin and the two associated proteins h1 03p (hGCP2) and h103p (hGCP3) are essential. These proteins are also presen t in soluble complexes containing additional polypeptides. Partial sequenci ng of a 76-kD polypeptide band from these complexes allowed the isolation o f a cDNA encoding for a new protein (h76p = hGCP4) expressed ubiquitously i n mammalian tissues. Orthologues of h76p have been characterized in Drosoph ilia and in the higher plant Medicago. Several pieces of evidence indicate that h76p is involved in microtubule nucleation. (1) h76p is localized at t he centrosome as demonstrated by immunofluorescence. (2) h76p and gamma-tub ulin are associated in the gamma-tubulin complexes. (3) gamma-tubulin compl exes containing h76p bind to microtubules. (4) h76p is recruited to the spi ndle poles and to Xenopus sperm basal bodies, (5) h76p is necessary for ast er nucleation by sperm basal bodies and recombinant h76p partially replaces endogenous 76p in oocyte extracts. Surprisingly, h76p shares partial seque nce identity with human centrosomal proteins h103p and h104p, suggesting a common protein core. Hence, human gamma-tubulin appears associated with at least three evolutionary related centrosomal proteins, raising new question s about their functions at the molecular level.