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

Abstract

SUMMARYCytoskeletal 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.

The actin-microtubule cross-linking activity ofDrosophilaShort stop is regulated by intramolecular inhibition

“…This type of cross-talk often requires mechanical coupling between the two cytoskeletal networks by proteins or protein complexes that act as physical cross-bridges (Salmon et al ., 2002; Rothenberg et al ., 2003; Wittmann et al ., 2003; Miller et al ., 2004; Rosales-Nieves et al ., 2006; Lee and Suter, 2008; Applewhite et al ., 2010). The spectraplakins are one such family of giant cytoskeletal cross-linking proteins that have been highly conserved across most animal lineages (Lee et al ., 2000; Röper et al ., 2002; Röper and Brown, 2003; Jefferson et al ., 2004; Sonnenberg and Liem, 2007; Kim et al ., 2011; Suozzi et al ., 2012). Wherever studied genetically, spectraplakins are found to be essential genes that play multiple roles in development.…”

Transcriptionally regulated cell adhesion network dictates distal tip cell directionality

“…Previous work has shown that when DTCs migrate dorsally on the hypodermal BM, the DTC forms a single lamellipodium in the direction of migration and then retracts its trailing edge as it shifts its migration to the dorsal BM (Kim et al, 2011). This mode of migration may depend on the contractile activity of NMY-2 and could be necessary for the DTC to transition from the hypodermal BM to the dorsal BM.…”

Nuclear positioning in the gonadal distal tip cells of C. elegans

“…Each DTC forms a close-fitting cap over the 6–10 germ cells and had been thought to maintain this morphology during the course of its migration 2 . Unexpectedly, however, DTCs were found to change their shape dramatically at the first turn 3 . DTCs that expressed GFP-moesin, which labels cortical actin filaments, were analyzed by confocal microscopy and shown to extend a single large lamellipodium dorsally when they make the first turn (Fig.…”

“…The DTCs extend lamellipodia at the onset of this turn and thus place their nuclei near the leading edge. This nuclear translocation requires the action of VAB-10B1, one of the spectraplakin isoforms in C. elegans 3 . Spectraplakins are large cytoplasmic proteins that regulate the cytoskeleton 4 - 6 .…”

“…Nuclear translocation in DTCs is suppressed in mutants lacking VAB-10B1. Although the network of F-actin is mostly normal in these animals, the microtubule (MT) network is severely disrupted 3 . VAB-10B1 has an N-terminal actin-binding domain (ABD), which is followed by a plakin domain, spectrin repeats, and an MT-binding domain (MTBD).…”