Spindles (green) in Axs mutants (right) are barrel shaped and lose symmetric chromosome (blue) alignment.

Hawley/Macmillan

Arecent report by Joseph Kramer and Scott Hawley (Stowers Institute for Medical Research, Kansas City, MO) demonstrates that a widely conserved protein regulates meiotic spindle formation from a peculiar membranous structure surrounding the spindle.Nearly two decades ago, sheath-like membranes resembling the endoplasmic reticulum (ER) were seen enclosing the meiotic spindle in wolf spider spermatocytes. The structures have remained mysterious—no function has been assigned to them, and they have not been identified in any other system. Kramer and Hawley have now not only found the sheath in fly oocytes, but also identified the protein Axs as a component of the structure.

Mutations in Axs are known to cause segregation defects in chromosomes that do not crossover during meiosis. The authors cloned the gene and found that Axs is an ER-localized protein that also surrounds the meiotic spindle in a structure much like the one seen in spermatocytes. The sheath may be formed from a subset of the ER, as constitutive ER proteins such as BiP were lacking.

In cells expressing a dominant–negative version of Axs, the meiotic spindle was unusually barrel shaped—microtubules were wider at the midzone. Kramer suggests that the sheath may serve as a sort of girdle that restrains the spindle during its formation. The mutation also somehow caused both homologues of nonexchange chromosomes to align on the same side of the metaphase plate, thus explaining the nondisjunction phenotype of Axs mutants.

Oocytes with these defects were unable to maintain the metaphase I arrest that normally delays egg maturation until surrounding somatic cells signal that the time is right. “Axs is a transmembrane protein not so different from a number of receptor proteins,” says Hawley. “Maybe it regulates meiotic progression as a receptor for oocyte–somatic cell crosstalk by telling chromosomes to stay in metaphase I until the egg is activated.” ▪

Reference:

Kramer, J., et al.
2003
.
Nat. Cell Biol.
5
:
261
–263.