Academic journal article Genetics

Class I Myosins Have Overlapping and Specialized Functions in Left-Right Asymmetric Development in Drosophila

Academic journal article Genetics

Class I Myosins Have Overlapping and Specialized Functions in Left-Right Asymmetric Development in Drosophila

Article excerpt

THE class I myosin genes encode myosin heavy chains, which are conserved in phylogenetically diverse organisms (Sellers 2000; Krendel and Mooseker 2005). The class I myosins are nonfilamentous, actin-based motor proteins and were the first discovered unconventional myosin proteins. These myosins are involved in a variety of cellular processes, such as cell migration, cell adhesion, and cell growth, through their regulation of actin dynamics, endocytosis, and signal transduction (Osherov and May 2000; Krendel and Mooseker 2005; Kim and Flavell 2008; McConnell and Tyska 2010).

The structure of the myosin I heavy chains is evolutionarily conserved and composed of head (or motor), neck, and tail domains (Figure 1A) (Coluccio 1997; Barylko et al. 2000). The head domain binds to filamentous (F)-actin and adenosine triphosphate (ATP), a common feature of myosin proteins (Figure 1A) (Mermall et al. 1998); the neck domain possesses one or more IQ motifs, which directly interact with calmodulin or calmodulin-related myosin light chains (Coluccio 1997; Barylko et al. 2000), and the tail domains are divided into short and long types. Short tails contain a single tail homology 1 (TH1) domain, which is rich in basic residues and thought to interact with plasma membranes (Coluccio 1997; Barylko et al. 2000); while long tails contain the TH1 domain; a tail homology 2 (TH2) domain, which is proline-rich and binds to F-actin in an ATP-independent manner; and a tail homology 3 (TH3), or Src homology 3 (SH3) domain, at the C terminus (Coluccio 1997; Barylko et al. 2000).

In single-celled eukaryotes that have multiple myosin I genes, redundant roles of these genes have been reported (Novak et al. 1995; Geli and Riezman 1996; Goodson et al. 1996; Jung et al. 1996). Saccharomyces cerevisiae encodes two class I myosins that function redundantly in growth and endocytosis (Geli and Riezman 1996; Goodson et al. 1996), and Dictyostelium encodes multiple class I myosins I with overlapping functions in macropinocytosis (Novak et al. 1995; Jung et al. 1996). Eight class I myosins are expressed in humans and mice (Berg et al. 2001). Myosin IA is thought to maintain brush border structure and membrane tension and to power the release of vesicles from the tips of microvilli (Tyska et al. 2005; McConnell et al. 2009; Nambiar et al. 2009), while Myosin IB regulates the actin-dependent post-Golgi trafficking of cargo (Almeida et al. 2011). Myosin IC is involved in vesicle transport both in the fertilized egg of Xenopus and in mammalian cells (Bose et al. 2002; Sokac et al. 2006; Fan et al. 2012) and regulates ion channels in the hair cells of the inner ear (Gillespie and Cyr 2004). Interestingly, an isoform of Myosin IC localizes to the nucleus and contributes to transcription (Pestic-Dragovich et al. 2000; Philimonenko et al. 2004), and Myosin IF is involved in neutrophil migration (Kim et al. 2006). In addition, mutations in Myosin IA, Myosin IC, and Myosin IF are associated with hereditary hearing loss (Chen et al. 2001; Donaudy et al. 2003; Zadro et al. 2009). In vertebrates, each class I myosin is expressed in various cell types and has distinct functions that depend on their cellular context (Gillespie 2004; Philimonenko et al. 2004; Sokac et al. 2006). Even so, these multiple class I myosins are predicted to have overlapping functions, as found in yeast and Dictyostelium (Tyska et al. 2005; Nambiar et al. 2009; Chen et al. 2012), complicating the understanding of their in vivo roles (Kim and Flavell 2008). Thus, the knockout and analysis of multiple class I myosin genes in vertebrates would represent a major challenge.

Three class I myosin genes, Myo31DF, Myo61F,and Myo95E have been identified in Drosophila (Figure 1A) (Tzolovsky et al. 2002). Myo31DF and Myo61F are closely related to the mammalian Myosin ID and Myosin IC, respectively (Morgan et al. 1994; Berg et al. 2001). However, the head domain of Myo95E contains an atypical insertion (Figure 1A) (Tzolovsky et al. …

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