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You searched for subject:(bicaudal D). Showing records 1 – 2 of 2 total matches.

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University of California – San Francisco

1. Huynh, Walter. Disease-Associated Mutations in Human BICD2 Hyperactivate Motility of Dynein-Dynactin.

Degree: Biochemistry and Molecular Biology, 2017, University of California – San Francisco

Mammalian cytoplasmic dynein is a microtubule-based motor that is involved in many cellular functions, one of which includes the retrograde transport of cargo. In contrast to yeast dynein, which is processive on its own, mammalian dynein requires both an adaptor protein and dynactin in order to achieve micron long run-lengths. Bicaudal D2 (BICD2), a protein comprised of three distinct coiled-coils, is one such adaptor. Recent studies have reported that mutations in BICD2 are associated with neurodegenerative diseases that include spinal muscular atrophy. In this dissertation, I demonstrate through biochemical and single molecule microscopy assays that full-length BICD2 is auto-inhibited and can be activated to interact with dynein and dynactin via the addition of one of its interacting partners, Rab6a. Testing of four BICD2 disease-associated mutations with this same set of assays reveal that, compared to wild-type, the mutants exhibit an increased formation of motile motor complexes. I further confirm this finding by developing an in vitro cargo reconstitution assay using liposomes as proxies for vesicles. This apparent ability to increase transport by the mutants is also observed in cells using an inducible re-localization system with peroxisomes. When overexpressed in rat hippocampal neurons, the BICD2 mutants lead to decreased neurite growth. Altogether, this work shows that dominant mutations in BICD2 hyperactivate dynein-driven motility and suggest that an imbalance of minus versus plus end–directed microtubule motility in neurons may underlie spinal muscular atrophy.

Subjects/Keywords: Biochemistry; Bicaudal D; dynein; motor; spinal muscular atrophy; transport

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Huynh, W. (2017). Disease-Associated Mutations in Human BICD2 Hyperactivate Motility of Dynein-Dynactin. (Thesis). University of California – San Francisco. Retrieved from http://www.escholarship.org/uc/item/9p33d5tj

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Chicago Manual of Style (16th Edition):

Huynh, Walter. “Disease-Associated Mutations in Human BICD2 Hyperactivate Motility of Dynein-Dynactin.” 2017. Thesis, University of California – San Francisco. Accessed October 22, 2019. http://www.escholarship.org/uc/item/9p33d5tj.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

MLA Handbook (7th Edition):

Huynh, Walter. “Disease-Associated Mutations in Human BICD2 Hyperactivate Motility of Dynein-Dynactin.” 2017. Web. 22 Oct 2019.

Vancouver:

Huynh W. Disease-Associated Mutations in Human BICD2 Hyperactivate Motility of Dynein-Dynactin. [Internet] [Thesis]. University of California – San Francisco; 2017. [cited 2019 Oct 22]. Available from: http://www.escholarship.org/uc/item/9p33d5tj.

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation

Council of Science Editors:

Huynh W. Disease-Associated Mutations in Human BICD2 Hyperactivate Motility of Dynein-Dynactin. [Thesis]. University of California – San Francisco; 2017. Available from: http://www.escholarship.org/uc/item/9p33d5tj

Note: this citation may be lacking information needed for this citation format:
Not specified: Masters Thesis or Doctoral Dissertation


Universiteit Utrecht

2. Noordstra, I. The Role of Bicaudal D in motor protein mediated transport.

Degree: 2012, Universiteit Utrecht

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… Advisors/Committee Members: Akhmanova, A..

Subjects/Keywords: cytoskeleton; microtubules; actin filaments; intermediate filaments; myosin; kinesin; dynein; dynactin; bicaudal D

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APA · Chicago · MLA · Vancouver · CSE | Export to Zotero / EndNote / Reference Manager

APA (6th Edition):

Noordstra, I. (2012). The Role of Bicaudal D in motor protein mediated transport. (Masters Thesis). Universiteit Utrecht. Retrieved from http://dspace.library.uu.nl:8080/handle/1874/252588

Chicago Manual of Style (16th Edition):

Noordstra, I. “The Role of Bicaudal D in motor protein mediated transport.” 2012. Masters Thesis, Universiteit Utrecht. Accessed October 22, 2019. http://dspace.library.uu.nl:8080/handle/1874/252588.

MLA Handbook (7th Edition):

Noordstra, I. “The Role of Bicaudal D in motor protein mediated transport.” 2012. Web. 22 Oct 2019.

Vancouver:

Noordstra I. The Role of Bicaudal D in motor protein mediated transport. [Internet] [Masters thesis]. Universiteit Utrecht; 2012. [cited 2019 Oct 22]. Available from: http://dspace.library.uu.nl:8080/handle/1874/252588.

Council of Science Editors:

Noordstra I. The Role of Bicaudal D in motor protein mediated transport. [Masters Thesis]. Universiteit Utrecht; 2012. Available from: http://dspace.library.uu.nl:8080/handle/1874/252588

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