VAB-10 spectraplakin acts in cell and nuclear migration in Caenorhabditis elegans

Abstract

Cytoskeletal regulation is important in cell migration. The Caenorhabditis elegans gonadal distal tip cells (DTCs) offer a simple model with which to investigate the mechanism of cell migration in organogenesis. Here, we report that one of the spectraplakin isoforms, VAB-10B1, plays an essential role in cell and nuclear migration of DTCs by regulating the actin and microtubule (MT) cytoskeleton. In the vab-10(tk27) mutant, which lacks VAB-10B1, alignment of filamentous (F)-actin and MTs was weakly and severely disorganized, respectively, which resulted in a failure to translocate the DTC nucleus and a premature termination of DTC migration. An MT growing-tip marker, EBP-2-GFP, revealed that polarized outgrowth of MTs towards the nuclei of migrating DTCs was strikingly impaired in tk27 animals. A vab-10 mini-gene encoding only the actin-and MT-binding domains significantly rescued the gonadal defects, suggesting that VAB-10B1 has a role in linking actin and MT filaments. These results suggest that VAB-10B1/spectraplakin regulates the polarized alignment of MTs, possibly by linking F-actin and MTs, which enables normal nuclear translocation and cell migration of DTCs.

Noncentrosomal microtubules in C. elegans epithelia

“…Finally, not only BIN1 bridges CLIP-170 and nesprin, but it also interacts with actin -as nesprin does-suggesting that the tethering of the nucleus to both actin filaments and MTs by Amphyphisin-2/BIN1/ CeAMPH-1 is important for its proper positioning. This dual role of actin and MTs in nuclear positioning through a common cytolinker has also been observed during somatic gonad migration in C. elegans (Kim et al, 2011). The key role of the actin cytoskeleton is further evidenced by the identification of a SUN-KASHindependent pathway for nuclear migration (Chang et al, 2013), mediated by another conserved F-BARdomain containing protein called TOCA-1 (Transducer of CDC-42-dependent actin assembly).…”

“…This is the case for nuclear positioning and probably trafficking. The identification of the specific proteins, such as amphyphisin (D'Alessandro et al, 2015) and the spectraplakin VAB-10B (Kim et al, 2011) in nuclear positioning, or complexes, such as EXC-6 and possibly STRIPAK (Lant et al, 2015;Shaye and Greenwald, 2015) in trafficking, that bridge and coordinate both cytoskeletal networks, and of the signaling events taking place at such hubs will be important. In addition, a systematic investigation of the motor proteins acting in transport or positioning would be welcome.…”

“…The following fusion proteins with tubulin or MT-binding domains have been used: TBA-2::GFP (Quintin et al, 2016), VAB-10B(MTBD)::GFP (Kim et al, 2011), ensconsin-MTBD::3xGFP (Shaye and Greenwald, 2015), TBG-1::GFP and GIP-2::GFP (Feldman and Priess, 2012;Quintin et al, 2016;Wang et al, 2015). Tracking MT minus ends has mostly been achieved using TBG-1::GFP and GIP-2::GFP (Feldman and Priess, 2012;Quintin et al, 2016;Wang et al, 2015), and the 1TIP marker EBP-2::GFP has been used as a reporter of MT dynamics (Quintin et al, 2016;Shaye andGreenwald, 2015, Wang et al, 2015) which was initially developed in the early embryo by (Srayko et al, 2005).…”

Spectraplakin family proteins – cytoskeletal crosslinkers with versatile roles

“…Here, VAB-10B protects cells from internal shearing forces, as it likely anchors cortical actin to the MT network (Bosher et al, 2003). VAB-10B also directs nuclear translocation and cell migration in gonadal distal tip cell by mediating actin filament and MT crosslinking (Kim et al, 2011). Furthermore, a recent study demonstrated that VAB-10A can link the C. elegans fusogenic protein epithelial fusion failure 1 (EFF-1) to the F-actin network and so enhance cell-cell fusion (Yang et al, 2017).…”

Composite biopolymer scaffolds shape muscle nucleus: Insights and perspectives fromDrosophila

“…20 Shot, the only member of the plakin family in the fly genome, was originally identified as a provider of mechanical linkage between the cortical actin and MTs. 21,22 Similarly in C. elegans, the intracellular role of spectraplakins in nuclear anchoring and movement 23 seems to be more ancient. Interestingly, in a recent S2-cell based screen, nesprins and Shot were also identified as factors involved in nuclear morphology, 24 possibly indicating a more general role in protecting nuclei.…”