Abstract
Long-distance intracellular transport of organelles, mRNA, and proteins ("cargo") occurs along the microtubule cytoskeleton by the action of kinesin and dynein motor proteins, but the vast network of factors involved in regulating intracellular cargo transport are still unknown. We capitalize on the Drosophila melanogaster S2 model cell system to monitor lysosome transport along microtubule bundles, which require enzymatically active kinesin-1 motor protein for their formation. We use an automated tracking program and a naive Bayesian classifier for the multivariate motility data to analyze 15,683 gene phenotypes and find 98 proteins involved in regulating lysosome motility along microtubules and 48 involved in the formation of microtubule filled processes in S2 cells. We identify innate immunity genes, ion channels, and signaling proteins having a role in lysosome motility regulation and find an unexpected relationship between the dynein motor, Rab7a, and lysosome motility regulation.
Highlights
Numerous signaling cascades, receptors, and adaptor proteins appear to be involved in dictating the specificity of molecular motor activation/inactivation; an insufficient number of proteins have been identified to account for the complex regulation of motor activity and cargo transport (Kashina and Rodionov, 2005)
Long-distance intracellular transport of organelles, mRNA, and proteins (‘‘cargo’’) occurs along the microtubule cytoskeleton by the action of kinesin and dynein motor proteins, but the vast network of factors involved in regulating intracellular cargo transport are still unknown
We capitalize on the Drosophila melanogaster S2 model cell system to monitor lysosome transport along microtubule bundles, which require enzymatically active kinesin-1 motor protein for their formation
Summary
Receptors, and adaptor proteins appear to be involved in dictating the specificity of molecular motor activation/inactivation; an insufficient number of proteins have been identified to account for the complex regulation of motor activity and cargo transport (Kashina and Rodionov, 2005). While kinesin-1 binds Merlin via its light chain, it does not require the light chain to bind dFMR (Ling et al, 2004) or mitochondria (Bensenor et al, 2010); instead, it uses the adaptor protein Milton to bind a mitochondrial GTPase Miro (Glater et al, 2006). Such motility proteins are not identifiable using bioinformatics approaches because of their structural and sequence heterogeneity. Uncharacterized motility factors are likely to elude most protein-protein interaction assays as well, because of their large size and/or transient nature of these protein complexes
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