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

Mol Biol Cell. 2021 Mar 15;32(6):492-503. doi: 10.1091/mbc.E20-08-0559. Epub 2021 Jan 21.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aspergillus nidulans / metabolism
  • Basidiomycota / metabolism
  • Biological Transport
  • Dyneins / metabolism
  • Endoplasmic Reticulum / metabolism
  • Endosomes / metabolism
  • Fungal Proteins / metabolism*
  • Kinesins / metabolism
  • Metabolic Networks and Pathways
  • Microtubules / metabolism
  • Mitochondria / metabolism
  • Peroxisomes / metabolism*
  • Peroxisomes / physiology
  • Phosphoric Monoester Hydrolases / metabolism*
  • Protein Transport / genetics
  • Protein Transport / physiology*
  • Transport Vesicles / metabolism

Substances

  • Fungal Proteins
  • DipA protein, Aspergillus nidulans
  • Phosphoric Monoester Hydrolases
  • Dyneins
  • Kinesins

Supplementary concepts

  • Ustilago maydis