Roles for two partially redundant α‐tubulins during mitosis in early Caenorhabditis elegans embryos

Abstract

The Caenorhabditis elegans genome encodes multiple isotypes of alpha-tubulin and beta-tubulin. Roles for a number of these tubulins in neuronal development have been described, but less is known about the isoforms that function during early embryonic development. Microtubules are required for multiple events after fertilization produces a one-cell zygote in C. elegans, including pronuclear migration, mitotic spindle assembly and function, and proper spindle positioning. Here we describe a conditional and dominant mis-sense mutation in the C. elegans alpha-tubulin gene tba-1 that disrupts pronuclear migration and positioning of the first mitotic spindle, and results in a highly penetrant embryonic lethality, at the restrictive temperature of 26 degrees C. Our analysis of the dominant tba-1 (or346ts) allele suggests that TBA-1 assembles into microtubules in early embryonic cells. However, we also show that reduction of tba-1 function using RNA interference results in defects much less severe than those caused by the dominant or346ts mutation, due to partial redundancy of TBA-1 and another alpha-tubulin called TBA-2. Reducing the function of both TBA-1 and TBA-2 results in severe defects in microtubule-dependent processes. We conclude that microtubules in the early C. elegans embryo are composed of both TBA-1 and TBA-2, and that the dominant tba-1(or346ts) mutation disrupts MT assembly or stability. Cell Motil.

Microtubule-based localization of a synaptic calcium-signaling complex is required for left-right neuronal asymmetry in C. elegans

“…There are nine -tubulin and six -tubulin isoforms predicted in the C. elegans genome (C. elegans Sequencing Consortium, 1998). Previous studies suggested functional redundancy of some -and -tubulin isotypes (Driscoll et al, 1989;Lu et al, 2004;Phillips et al, 2004;Wright and Hunter, 2003). Nocodazole, which disrupts microtubule polymerization regardless of subunit composition, provides a convenient tool with which to analyze the function of microtubules in biological processes.…”

Specific α- and β-Tubulin Isotypes Optimize the Functions of Sensory Cilia inCaenorhabditis elegans

“…According to this model, multiple genes allow the maintenance of a stable pool of available monomers and dimers. The small amount of sequence variation within the a-and b-tubulin families supports this idea, as do studies of functionally redundant mitotic tubulins in C. elegans Lu et al 2004;Phillips et al 2004;Lu and Mains 2005). The alternative hypothesis proposes that specific structures, e.g., ciliary axonemes or axonal microtubules, rely on tubulins optimized for specific roles.…”

“…Some of these genes, particularly tba-1, tba-2, tbb-1, and tbb-2, are expressed broadly during embryogenesis and function redundantly in spindle assembly and positioning Lu et al 2004;Phillips et al 2004;Lu and Mains 2005). tba-1 and tbb-2 have also been recently shown to be important for axon outgrowth and synaptogenesis (Baran et al 2010).…”

Physics Models of Pronuclear Movements in Eggs

“…E.g. tac-1 is essential for pronuclear migration [10]; loss of function of the gamma-tubulin gene by RNAi does not affect pronuclear migration [11]; pronuclei treated with antibodies will not move at all [12][13]; some special biochemical treatments may [14] or may not [15][16][17] affect to the motion; mutant defected pronuclei migrate abnormally [18][19][20][21] or normally [22]. We think all of the above results are caused by normal or abnormal EMF (EF) distribution.…”