Contents

Search

retromer complex

Function: 1) regulates trafficking of type-1 membrane proteins from endosome to trans-Golgi 2) retrieves lysosomal enzyme receptors (IGF2R & M6PR) from endosomes to the trans-Golgi network 3) regulates transcytosis of the polymeric immunoglobulin receptor 4) regulates trafficking of VPS10 domain-containing proteins 5) APP, BACE, presenilin-1, & apoE among retromer complex cargo [3] 6) SorLA may be receptor for retromer complex [3] Structure: - consists of: - VPS2 - VPS26A or VPS26B - VPS29 - VPS35 - SNX1 - SNX2 Pathology: 1) reduced expression of retromer or its subunit VPS35 results in redistribution or mistrafficking of its cargo [2] 2) subunit VPS35 regulates Abeta peptide levels 3) expression diminished in spatiotemporal parallel with Alzheimer's disease (diminished expression conforms to spatiotemporal model of AD based upon Braak staging) Notes: - ref [4] discusses age-related pathways that interact with retromer function

Related

retromer complex (GO:0030904)

General

molecular complex

Properties

SUBUNITS: vacuolar protein sorting-associated protein 26A COMPARTMENT: endosome vacuolar protein sorting-associated protein 26B vacuolar protein sorting-associated protein 29 vacuolar protein sorting-associated protein 35 sorting nexin-1 COMPARTMENT: cytoplasm golgi MOTIF: Ser phosphorylation site {S32} Ser phosphorylation site {S39} Thr phosphorylation site {T41} PX domain {143-272} MOTIF: SH3-binding site NAME: SH3-binding site Ser phosphorylation site {S188} sorting nexin-2 MOTIF: Ser phosphorylation site {S119} PX domain {140-269} MOTIF: SH3-binding site NAME: SH3-binding site Ser phosphorylation site {S185} Ser phosphorylation site {S277}

References

  1. UniProt :accession Q9UBQ0
  2. Small SA, Kent K, Pierce A, Leung C, Kang MS, Okada H, Honig L, Vonsattel JP, Kim TW. Model-guided microarray implicates the retromer complex in Alzheimer's disease. Ann Neurol. 2005 Dec;58(6):909-19. PMID: 16315276
  3. Verges M., Luton F., Gruber C., Tiemann F., Reinders L.G., Huang L., Burlingame A.L., Haft C.R., Mostov K.E.; The mammalian retromer regulates transcytosis of the polymeric immunoglobulin receptor Nat Cell Biol 2004, 6:763-769 PMID: 15247922
  4. Wilson KA The understudied links of the retromer complex to age-related pathways. GeroScience. 2022. 44, 19-24 https://link.springer.com/article/10.1007/s11357-021-00430-1

Components

sorting nexin-1 (SNX1) sorting nexin-2; transformation-related gene 9 protein; TRG-9 (SNX2) vacuolar protein sorting-associated protein 26A (vesicle protein sorting 26A, hVPS26A, VPS26A, VPS26) vacuolar protein sorting-associated protein 26B (vesicle protein sorting 26B, hVPS26B, VPS26B) vacuolar protein sorting-associated protein 29 (vesicle protein sorting 29, hVPS29, DC7, PEP11, VPS29) vacuolar protein sorting-associated protein 35 (vesicle protein sorting 35, hVPS35, maternal-embryonic 3, VPS35, MEM3, TCCCTA00141)