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Molecular Mechanisms of Microtubule-Based Transport in a Genetic Model System
Driscoll, Bellana
Driscoll, Bellana
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Abstract
Intracellular cargos such as organelles and vesicles move on microtubules by motor-driven transport. The canonical mode of microtubule-based transport is that adaptor proteins are required to link cargos to motors (kinesins or dynein). An alternative mode was discovered in which peroxisomes move by hitchhiking in the filamentous fungi Aspergillus nidulans. Hitchhiking involves transient tethering of peroxisomes to early endosomes attached to motor proteins. In this schematic, the early endosomes comigrate with peroxisome at the leading edge to “pull” the cargo; it requires the recruitment of a linker protein PxdA as well as its cofactor DipA phosphatase. To better understand the mechanisms of hitchhiking, I conducted phenotypic mutagenesis screens in A. nidulans, identifying 7 positive hits. I was able to pursue two hits further, JSA216 and JSA217. JSA216 mutation is a G44V substitution localized to AN6372, a highly disordered and uncharacterized protein. JSA217 mutation is a C106R substitution in an Aspergillus kinesin-3 called UncA, one of the three major classes of cargo-carrying kinesins. These data indicate areas of further research to discern the hitchhiking machinery in this genetic model filamentous fungus.
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2023-01-01