The Role of Bicaudal D in motor protein mediated transport
Year: 2012
Type: dissertation
Abstract: A highly important and comprehensive mechanism within the cell is the proper distribution of \nproteins, lipids, mRNA’s and cell organelles to various destinations in the cellular matrix. In \norder to fulfil this task, cells make use of their network of fibers extending throughout the \ncytoplasm. Two types of fibers involved in cellular transport are microtubules and actin \nfilaments which differ in mechanical properties, dynamics and biological roles (Campbell & \nReece., 2005). Many proteins are known to regulate these cytoskeletal filaments by either \nsupport their generation or degradation (Alberts et al., 2008). \nMolecular motors use the polarized cytoskeletal filaments as rails on which they \nconvey different cargoes. They differ in the filament track they bind, in the direction they \nmove and in the cargo they transport. Three major classes of motor proteins have been \nidentified: myosins, kinesins and dyneins. Myosins are plus-end directed actin binding motor \nproteins. They are, inter alia, responsible for muscle contraction. Also kinesins are plus-end \ndirected motor proteins. However, they use microtubules as a rail to transport their cargo. \nDyneins are a group of motor proteins which transports their cargo towards the minus-ends \nof microtubules. They are known to be the largest and the fastest among the molecular \nmotors (Schliwa & Woelkhe, 2003). Dyneins are devided into two subclasses; axonemal \ndynein which is involved in the motion of cilia and flagella (Campbell & Reece, 2005), and \ncytoplasmic dynein which is responsible for almost all minus-end directed transport in the \ncytoplasm (Alberts et al., 2008). Cytoplasmic dynein often functions together with dynactin. \nDynactin is a protein complex that modulates binding of dynein to cargoes which have to be \ntransported along microtubules. In addition, dynactin also enhances the processivity of \ncytoplasmic dynein (Alberts et al., 2008). \nMultiple factors are found to contribute to the recruitment of dynein and dynactin to \nspecific cargoes. A well studied cargo linking factor is Bicaudal D (BICD). BICD is a \ncytoplasmic coiled-coil protein which is found in Drosophila, C. elegans and mammals \n(BICD1 and BICD2) (Baens & Marynen, 1997; Fridolfsson et al., 2010; Fumoto et al., 2006). \nIn Drosophila, BICD and its binding partner Egalitarian (Egl) play important roles in \noogenesis and embryogenesis. They are shown to be critical in mRNA distribution during \nseveral stages of development. In mammalian cells BICD2 acts as a linker protein between \ndynein/dynactin complexes and membrane vesicles. The BICD2 N-terminus is able to bind \nthe motor protein whereas the C-terminus recognizes and binds Rab6 coated vesicles \n(Dienstbier & Li, 2009). In addition, several studies show that BICD acts as a regulator of bidirectional \ntransport of the nucleus by dynein and kinesin-1 (Tanenbaum et al., 2011). \nAlthough BICD shows great affinity for dynein/dynactin and Rab6 coated vesicles, \nalso other BICD binding proteins, including the motor protein kinesin-1, were identified \n(Grigoriev et al., 2007). This suggests that BICD not only functions as a linker protein, but \nalso coordinates the transport of cargoes via different motor proteins.
Author: Ivar Noordstra
Language: English
Subfield: Cell Biology
Domain: Life Sciences
Open Access status: green
OpenAlex ID: W3649879