BEACH domain proteins function as cargo-sorting adaptors in secretory and endocytic pathways

J Cell Biol. 2024 Dec 2;223(12):e202408173. doi: 10.1083/jcb.202408173. Epub 2024 Nov 8.

Abstract

We identify BEACH domain-containing proteins (BDCPs) as novel membrane coat proteins involved in the sorting of transmembrane proteins (TMPs) on the trans-Golgi network and tubular sorting endosomes. The seven typical mammalian BDCPs share a predicted alpha-solenoid-beta propeller structure, suggesting they have a protocoatomer origin and function. We map the subcellular localization of seven BDCPs based on their dynamic colocalization with RAB and ARF small GTPases and identify five typical BDCPs on subdomains of dynamic tubular-vesicular compartments on the intersection of endocytic recycling and post-Golgi secretory pathways. We demonstrate that BDCPs interact directly with the cytosolic tails of selected TMPs and identify a subset of TMPs, whose trafficking to the plasma membrane is affected in cells lacking BDCP. We propose that the competitive binding of BDCPs and clathrin coat adaptors to the cytosolic tails of TMPs, followed by their clustering to distinct subdomains of secretory/recycling tubules function as a mechanism for sorting of TMPs in pleomorphic tubular-vesicular compartments that lack a clathrin coat.

MeSH terms

  • ADP-Ribosylation Factors / genetics
  • ADP-Ribosylation Factors / metabolism
  • Adaptor Proteins, Vesicular Transport / genetics
  • Adaptor Proteins, Vesicular Transport / metabolism
  • Animals
  • Cell Membrane / metabolism
  • Endocytosis*
  • Endosomes* / metabolism
  • HeLa Cells
  • Humans
  • Membrane Proteins / genetics
  • Membrane Proteins / metabolism
  • Protein Binding
  • Protein Domains
  • Protein Transport*
  • Secretory Pathway
  • rab GTP-Binding Proteins / genetics
  • rab GTP-Binding Proteins / metabolism
  • trans-Golgi Network* / metabolism

Substances

  • Membrane Proteins
  • ADP-Ribosylation Factors
  • rab GTP-Binding Proteins
  • Adaptor Proteins, Vesicular Transport