The Role of Bicaudal D in motor protein mediated transport

Abstract

A highly important and comprehensive mechanism within the cell is the proper distribution of proteins, lipids, mRNA’s and cell organelles to various destinations in the cellular matrix. In order to fulfil this task, cells make use of their network of fibers extending throughout the cytoplasm. Two types of fibers involved in cellular transport are microtubules and actin filaments which differ in mechanical properties, dynamics and biological roles (Campbell & Reece., 2005). Many proteins are known to regulate these cytoskeletal filaments by either support their generation or degradation (Alberts et al., 2008). Molecular motors use the polarized cytoskeletal filaments as rails on which they convey different cargoes. They differ in the filament track they bind, in the direction they move and in the cargo they transport. Three major classes of motor proteins have been identified: myosins, kinesins and dyneins. Myosins are plus-end directed actin binding motor proteins. They are, inter alia, responsible for muscle contraction. Also kinesins are plus-end directed motor proteins. However, they use microtubules as a rail to transport their cargo. Dyneins are a group of motor proteins which transports their cargo towards the minus-ends of microtubules. They are known to be the largest and the fastest among the molecular motors (Schliwa & Woelkhe, 2003). Dyneins are devided into two subclasses; axonemal dynein which is involved in the motion of cilia and flagella (Campbell & Reece, 2005), and cytoplasmic dynein which is responsible for almost all minus-end directed transport in the cytoplasm (Alberts et al., 2008). Cytoplasmic dynein often functions together with dynactin. Dynactin is a protein complex that modulates binding of dynein to cargoes which have to be transported along microtubules. In addition, dynactin also enhances the processivity of cytoplasmic dynein (Alberts et al., 2008). Multiple factors are found to contribute to the recruitment of dynein and dynactin to specific cargoes. A well studied cargo linking factor is Bicaudal D (BICD). BICD is a cytoplasmic coiled-coil protein which is found in Drosophila, C. elegans and mammals (BICD1 and BICD2) (Baens & Marynen, 1997; Fridolfsson et al., 2010; Fumoto et al., 2006). In Drosophila, BICD and its binding partner Egalitarian (Egl) play important roles in oogenesis and embryogenesis. They are shown to be critical in mRNA distribution during several stages of development. In mammalian cells BICD2 acts as a linker protein between dynein/dynactin complexes and membrane vesicles. The BICD2 N-terminus is able to bind the motor protein whereas the C-terminus recognizes and binds Rab6 coated vesicles (Dienstbier & Li, 2009). In addition, several studies show that BICD acts as a regulator of bidirectional transport of the nucleus by dynein and kinesin-1 (Tanenbaum et al., 2011). Although BICD shows great affinity for dynein/dynactin and Rab6 coated vesicles, also other BICD binding proteins, including the motor protein kinesin-1, were identified (Grigoriev et al., 2007). This suggests that BICD not only functions as a linker protein, but also coordinates the transport of cargoes via different motor proteins.