Functional interplay between LIS1, NDE1 and NDEL1 in dynein-dependent organelle positioning

Abstract

Cytoplasmic dynein 1 is a minus-end-directed microtubule motor that is required for a wide range of activities involving movement or anchoring of cellular structures (Vallee et al., 2004). These activities include separation of chromosomes during mitosis, cell migration, and the movement and localisation of substrates such as mRNAs, signalling complexes and membrane organelles. To understand how dynein function over such a diverse range of activities is regulated, much attention has focussed on the composition of the dynein motor complex and the roles of accessory proteins.Dynein can be purified as a 1.6 MDa complex. This contains two copies of a motor subunit (dynein heavy chain; DHC), each of which comprises an AAA ATPase region involved in force generation and a stem region that connects the ATPase to the remaining, regulatory and cargo-binding subunits of the dynein complex. These subunits include dynein intermediate chain (DIC), dynein light intermediate chain (DLIC), and dynein light chains (DLCs) (Pfister et al., 2006). Dynein engages several accessory proteins or protein complexes, which might regulate its motor and/or cargo-binding activities. The best characterised of these is dynactin, a multiprotein complex that is almost universally associated with dynein-dependent functions (Schroer, 2004). More recently, several additional dynein-interacting proteins have been identified using a screen for Aspergillus nidulans mutants that are defective for nuclear distribution. These include NudF (Xiang et al., 1995) and NudE (Efimov and Morris, 2000), the higher eukaryote counterparts of which are Lissencephaly1 (LIS1) and NDE1, respectively. An NDE1-related protein, NDEL1 (also referred to as NudEL) has also been identified Sasaki et al., 2000). LIS1 interacts directly with DHC via sites on the first AAA domain and the stem region (Sasaki et al., 2000;Tai et al., 2002), with DIC (Tai et al., 2002), and with the p50 subunit of dynactin (Tai et al., 2002). NDEL1 and NDE1 also bind to dynein. However, the mode of binding might not be conserved here, because NDEL1 has been reported to bind HC (Sasaki et al., 2000), whereas NDE1 binds to DIC and the LC8 isoform of DLC (Stehman et al., 2007). In addition, NDE1 (Efimov and Morris, 2000;Feng et al., 2000) and NDEL1 (Derewenda et al., 2007;Niethammer et al., 2000;Sasaki et al., 2000) bind to LIS1 directly, and to each other (Bradshaw et al., 2009). There are currently two models to explain how these effectors modulate dynein function. They might regulate dynein motor activity directly (Mesngon et al., 2006;Yamada et al., 2008), or they might have a role in targeting dynein to cargoes (Liang et al., 2007;Vergnolle and Taylor, 2007).LIS1, NDE1 and NDEL1 have been implicated in many dyneinmediated activities, including cell migration, (Ding et al., 2009;Dujardin et al., 2003;Feng and Walsh, 2004;Kholmanskikh et al., 2003;Sasaki et al., 2005;Shu et al., 2004;Tanaka et al., 2004;Tsai et al., 2007;Tsai et al., 2005) , 2008). Mutations in or haplo-insufficiency of mammalian...

Lis1 mediates planar polarity of auditory hair cells through regulation of microtubule organization

“…In cultured cells, Lis1 and dynein regulate organelle position (Harada et al, 1998;Lam et al, 2010). We therefore determined whether the distributions of the Golgi and mitochondria were perturbed in Lis1 cKO-late hair cells.…”

Regulation of dynein localization and centrosome positioning by Lis-1 and asunder during Drosophila spermatogenesis

“…Localizations of LIS-1 and dyneindynactin within cells have been shown in several cases to be dependent on each other, although their interdependency varies with the model system and subcellular sites (Cockell et al, 2004;Coquelle et al, 2002;Lam et al, 2010;Lee et al, 2003). We examined localization of dynein-dynactin complexes in Lis-1 k11702 male germ cells using antibodies against dynein heavy chain and transgenic expression of DMN-GFP (McGrail and Hays, 1997).…”

Functional coupling of microtubules to membranes – implications for membrane structure and dynamics

“…A clear example of this comes from studies on nuclear distribution protein E (NDE1) and NDE1-like proteins. These two proteins appear to act redundantly with regard to membrane motility (Lam et al, 2010). Intriguingly, they not only affect dynein activity but are also required for maintaining the association of dynein with membranes (Lam et al, 2010).…”

“…These two proteins appear to act redundantly with regard to membrane motility (Lam et al, 2010). Intriguingly, they not only affect dynein activity but are also required for maintaining the association of dynein with membranes (Lam et al, 2010). NDE1 and Nudel (also known as NDEL1) both act in the recruitment of LIS1 (for lissencephaly-1) to membranes (Liang et al, 2004;Lam et al, 2010).…”