PxdA interacts with the DipA phosphatase to regulate peroxisome hitchhiking on early endosomes

John Salogiannis; Jenna R. Christensen; Livia D. Songster; Adriana Aguilar-Maldonado; Nandini Shukla; Samara L. Reck-Peterson

doi:10.1091/MBC.E20-08-0559

PxdA interacts with the DipA phosphatase to regulate peroxisome hitchhiking on early endosomes

John Salogiannis, Jenna R. Christensen, Livia D. Songster, Adriana Aguilar-Maldonado, Nandini Shukla, Samara L. Reck-Peterson^*

^*Corresponding author for this work

Molecular Biosciences

Research output: Contribution to journal › Article › peer-review

11 Scopus citations

Abstract

In canonical microtubule-based transport, adaptor proteins link cargoes to dynein and kinesin motors. Recently, an alternative mode of transport known as “hitchhiking” was discovered, where cargoes achieve motility by hitching a ride on already-motile cargoes, rather than attaching to a motor protein. Hitchhiking has been best studied in two filamentous fungi, Aspergillus nidulans and Ustilago maydis. In U. maydis, ribonucleoprotein complexes, peroxisomes, lipid droplets (LDs), and endoplasmic reticulum hitchhike on early endosomes (EEs). In A. nidulans, peroxisomes hitchhike using a putative molecular linker, peroxisome distribution mutant A (PxdA), which associates with EEs. However, whether other organelles use PxdA to hitchhike on EEs is unclear, as are the molecular mechanisms that regulate hitchhiking. Here we find that the proper distribution of LDs, mitochondria, and preautophagosomes do not require PxdA, suggesting that PxdA is a peroxisome-specific molecular linker. We identify two new pxdA alleles, including a point mutation (R2044P) that disrupts PxdA's ability to associate with EEs and reduces peroxisome movement. We also identify a novel regulator of peroxisome hitchhiking, the phosphatase DipA. DipA colocalizes with EEs and its association with EEs relies on PxdA. Together, our data suggest that PxdA and the DipA phosphatase are specific regulators of peroxisome hitchhiking on EEs.

Original language	English (US)
Pages (from-to)	492-503
Number of pages	12
Journal	Molecular biology of the cell
Volume	32
Issue number	6
DOIs	https://doi.org/10.1091/MBC.E20-08-0559
State	Published - Mar 1 2021

Funding

We thank Stephen A. Osmani for personal communication and sharing unpublished data on DipA and Thomas L. Schwarz for his guidance and supervision of J.S. for part of this project. We also thank the Nikon Imaging Centers at Harvard Medical School and University of California, San Diego for technical support and advice, Ross Tomaino and the Taplin Mass Spectrometry Facility at Harvard Medical School for technical support on mass spectrometry experiments, and the Bioinformatics Department at the Harvard T.H. Chan School of Public Health for assisting with whole-genome sequencing data analysis. J.S. was funded for part of this work by the Charles King Trust Fellowship supported by the Charles H. Hood Foundation (Boston, MA). J.R.C. was funded by a postdoctoral fellowship from the National Institutes of Health (Grant no. F32GM-126692). S.L.R.-P. is an investigator of the Howard Hughes Medical institute and is also supported by Grant no. R01GM-121772.

ASJC Scopus subject areas

Molecular Biology
Cell Biology

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10.1091/MBC.E20-08-0559

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title = "PxdA interacts with the DipA phosphatase to regulate peroxisome hitchhiking on early endosomes",

abstract = "In canonical microtubule-based transport, adaptor proteins link cargoes to dynein and kinesin motors. Recently, an alternative mode of transport known as “hitchhiking” was discovered, where cargoes achieve motility by hitching a ride on already-motile cargoes, rather than attaching to a motor protein. Hitchhiking has been best studied in two filamentous fungi, Aspergillus nidulans and Ustilago maydis. In U. maydis, ribonucleoprotein complexes, peroxisomes, lipid droplets (LDs), and endoplasmic reticulum hitchhike on early endosomes (EEs). In A. nidulans, peroxisomes hitchhike using a putative molecular linker, peroxisome distribution mutant A (PxdA), which associates with EEs. However, whether other organelles use PxdA to hitchhike on EEs is unclear, as are the molecular mechanisms that regulate hitchhiking. Here we find that the proper distribution of LDs, mitochondria, and preautophagosomes do not require PxdA, suggesting that PxdA is a peroxisome-specific molecular linker. We identify two new pxdA alleles, including a point mutation (R2044P) that disrupts PxdA's ability to associate with EEs and reduces peroxisome movement. We also identify a novel regulator of peroxisome hitchhiking, the phosphatase DipA. DipA colocalizes with EEs and its association with EEs relies on PxdA. Together, our data suggest that PxdA and the DipA phosphatase are specific regulators of peroxisome hitchhiking on EEs.",

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PxdA interacts with the DipA phosphatase to regulate peroxisome hitchhiking on early endosomes

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