Subpixel colocalization reveals amyloid precursor protein-dependent kinesin-1 and dynein association with axonal vesicles.

Proceedings of the National Academy of Sciences of the United States of America
Lukasz SzpankowskiLawrence S B Goldstein

Abstract

Intracellular transport of vesicles and organelles along microtubules is powered by kinesin and cytoplasmic dynein molecular motors. Both motors can attach to the same cargo and thus must be coordinated to ensure proper distribution of intracellular materials. Although a number of hypotheses have been proposed to explain how these motors are coordinated, considerable uncertainty remains, in part because of the absence of methods for assessing motor subunit composition on individual vesicular cargos. We developed a robust quantitative immunofluorescence method based on subpixel colocalization to elucidate relative kinesin-1 and cytoplasmic dynein motor subunit composition of individual, endogenous amyloid precursor protein (APP) vesicles in mouse hippocampal cells. The resulting method and data allow us to test a key in vivo prediction of the hypothesis that APP can recruit kinesin-1 to APP vesicles in neuronal axons. We found that APP levels are well-correlated with the amount of the light chain of kinesin-1 (KLC1) and the heavy chain of cytoplasmic dynein (DHC1) on vesicles. In addition, genetic reduction of APP diminishes KLC1 and DHC1 levels on APP cargos. Finally, our data reveal that reduction of KLC1 leads to decreased le...Continue Reading

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May 28, 2013·Human Molecular Genetics·Shermali GunawardenaLawrence S B Goldstein
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