davies2018: AP-4 vesicles contribute to spatial control of autophagy via...

davies2018R Documentation

AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A

Description

Data from 'AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A' Nature Communications.

Adaptor protein 4 (AP-4) is an ancient membrane trafficking complex, whose function has largely remained elusive. In humans, AP-4 deficiency causes a severe neurological disorder of unknown aetiology. We apply unbiased proteomic methods, including 'Dynamic Organellar Maps', to find proteins whose subcellular localisation depends on AP-4. We identify three transmembrane cargo proteins, ATG9A, SERINC1 and SERINC3, and two AP-4 accessory proteins, RUSC1 and RUSC2. We demonstrate that AP-4 deficiency causes missorting of ATG9A in diverse cell types, including patient-derived cells, as well as dysregulation of autophagy. RUSC2 facilitates the transport of AP-4-derived, ATG9A-positive vesicles from the trans-Golgi network to the cell periphery. These vesicles cluster in close association with autophagosomes, suggesting they are the 'ATG9A reservoir' required for autophagosome biogenesis. Our study uncovers ATG9A trafficking as a ubiquitous function of the AP-4 pathway. Furthermore, it provides a potential molecular pathomechanism of AP-4 deficiency, through dysregulated spatial control of autophagy.

Usage

  data("davies2018ap4b1")
  data("davies2018ap4e1")
  data("davies2018wt")

Format

The data is an instance of class MSnSet from package MSnbase.

References

AP-4 vesicles contribute to spatial control of autophagy via RUSC-dependent peripheral delivery of ATG9A Alexandra K. Davies, Daniel N. Itzhak, James R. Edgar, Tara L. Archuleta, Jennifer Hirst, Lauren P. Jackson, Margaret S. Robinson & Georg H. H. Borner https://doi.org/10.1038/s41467-018-06172-7

Examples

  data(davies2018wt)
  davies2018wt
  pData(davies2018wt)
  exprs(davies2018wt)[1:3,1:3]

  library("pRoloc")
  plot2D(davies2018wt,, main = "Davies 2018 HeLa - wt")

lgatto/pRolocdata documentation built on Oct. 17, 2024, 10:16 p.m.