Interplay Between Spindle Architecture and Function - International Review of Cell and Molecular Biology - page 108

In metazoans, the details of spindle architecture are not as well under-
stood, and their striking diversity implies significant architectural differences
( Fig. 3.6 ). Serial section electron microscopy has provided insight into spin-
dle architecture in a Ptk1 cell, revealing well-defined populations of astral,
spindle, and k-fiber MTs ( Mastronarde et al., 1993 ). In C. elegans , chromo-
somes are holocentric, meaning that the entire face of each chromosome
functions as a kinetochore, leading to a different partitioning of MT
populations ( Maddox et al., 2004 ). Embryo spindles of sea urchin and related
echinoderms possess prolific astral MTs with centrosomes closely associated
with spindle poles. The distance between centrosomes and spindle poles var-
ies considerably among cell types and species. Other variations on spindle
size and morphology appear with every comparative analysis of spindle mor-
phology, and correlations with genomic sequence and expression data may
provide clues to the molecular basis of these variations.
TPX2, a mediator of chromatin-directed spindle assembly discussed ear-
lier, provides one example of a spindle factor whose sequence and precise
function vary among species. TPX2 homologs have been investigated in
C. elegans (TPXL-1), Drosophila melanogaster (D-TPX2/Mei38/Ssp1), as
well as in Xenopus species, but in the absence of EM data, only spindle mor-
phology and not detailed architectural features can be compared. In all cases,
TPX2 is important to assemble a properly organized spindle. In Drosophila,
D-TPX2 is nonessential and its deletion/knockdown leads to a short spindle
phenotype. D-TPX2 localizes to k-fibers in meiotic and somatic Drosophila
cells, implicating its function on this population of MTs ( Goshima, 2011 ). In
C . elegans , knockdown of TPXL-1 also decreases spindle size but the protein
is enriched at the poles of the spindle and its abundance correlates with cen-
trosome size and spindle length ( Greenan et al., 2010 ). In contrast, TPX2 is
essential for spindle formation in Xenopus egg extracts, where it is an impor-
tant component of the Ran pathway of chromatin-dependent spindle
assembly ( Gruss et al., 2001; Wittmann et al., 2000 ), and RNAi studies in
human cells further indicate a requirement for TPX2 for spindle formation
( Gruss et al., 2002 ). Interestingly, the C. elegans and Drosophila TPX2-like
proteins possess only a subset of the functional domains found in vertebrate
TPX2, and each contains domains not found in the vertebrate homologs
( Goshima, 2011 ). Evolutionarily, one could imagine this protein may have
adapted to perform different spindle-related functions in each of these
organisms, potentially indicating one mechanism by which spindle architec-
ture is tuned to each species.