Intracellular transport is an essential function in eucaryotic cells, facilitated by motor proteins—proteins converting chemical energy into kinetic energy. It is understood that motorproteins work in teams enabling unidirectional and bidirectional transport of intracellularcargo over long distances. Disruptions of the underlying transport mechanisms, oftencaused by mutations that alter single motor characteristics, are known to cause neurodegenerative diseases. For example, phosphorylation of kinesin motor domain at the serineresidue is implicated in Huntington’s disease, with a recent study of phosphorylated andphosphomimetic serine residues indicating lowered single motor stalling forces. In this article we report the effects of mutations of this nature on transport properties of cargo carriedby multiple wild-type and mutant motors. Results indicate that mutants with altered stallforces might determine the average velocity and run-length even when they are outnumbered by wild type motors in the ensemble. It is shown that mutants gain a competitiveadvantage and lead to an increase in the expected run-length when the load on the cargo isin the vicinity of the mutant’s stalling force or a multiple of its stalling force. A separate contribution of this article is the development of a semi-analytic method to analyze transport ofcargo by multiple motors of multiple types. The technique determines transition ratesbetween various relative configurations of motors carrying the cargo using the transitionrates between various absolute configurations. This enables a computation of biologicallyrelevant quantities like average velocity and run-length without resorting to Monte Carlosimulations. It can also be used to introduce alterations of various single motor parametersto model a mutation and to deduce effects of such alterations on the transport of a commoncargo by multiple motors. Our method is easily implementable and we provide a softwarepackage for general use.
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