Evidence map›Paper›PMID 22718909›Full record

ArticleMolecular biology of the cell2012

Differential recognition of a dileucine-based sorting signal by AP-1 and AP-3 reveals a requirement for both BLOC-1 and AP-3 in delivery of OCA2 to melanosomes.

Anand Sitaram, Megan K Dennis, Rittik Chaudhuri, Wilfredo De Jesus-Rojas, Danièle Tenza, Subba Rao Gangi Setty, Christopher S Wood, Elena V Sviderskaya, Dorothy C Bennett, Graça Raposo and 2 more

Abstract read
In one paragraph

Article in Molecular biology of the cell, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 48 papers.

0numbers the graph read from it
0cells of the map it votes in
48citing papers in PubMed
2.4field-weighted citation impact, top 12% of its field
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

48 citing papers in PubMed, 67 citations in OpenAlex.

  1. Review
  2. Article
  3. Lysosome-related organelles orchestrate guanine crystal formation in pigment cells.Proceedings of the National Academy of Sciences of the United States of America · 2026
    Article
  4. Article
  5. Review
  6. Review
  7. Article
  8. Article
  9. Amelanotic Melanoma-Biochemical and Molecular Induction Pathways.International journal of molecular sciences · 2024
    Review
  10. Review
  11. Identification of Polymorphisms in theThe journal of poultry science · 2023
    Article
  12. Review
  13. Article
  14. Amorphigenin fromCurrent issues in molecular biology · 2022
    Article
  15. KIF13A-A Key Regulator of Recycling Endosome Dynamics.Frontiers in cell and developmental biology · 2022
    Review
  16. Melanosome Biogenesis in the Pigmentation of Mammalian Skin.Integrative and comparative biology · 2021
    Review
  17. Article
  18. AP-3-dependent targeting of flippase ATP8A1 to lamellar bodies suppresses activation of YAP in alveolar epithelial type 2 cells.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Review
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

12 authors at 4 institutions in 3 countries.

Anand SitaramDepartment of Pathology and Laboratory Medicine, University of Pennsylvania, Philadelphia, PA 19104, USA.
Megan K Dennis
Rittik Chaudhuri
Wilfredo De Jesus-Rojas
Danièle Tenza
Subba Rao Gangi Setty
Christopher S Wood
Elena V Sviderskaya
Dorothy C Bennett
Graça Raposo
Juan S Bonifacino
Michael S Marks
University of Pennsylvania · USCentre National de la Recherche Scientifique · FRNational Institutes of Health · USSt George's, University of London · GB

Funding

Protein Trafficking In The Endosomal-Lysosomal SystemZIAHD001607 · NICHD · EUNICE KENNEDY SHRIVER NATIONAL INSTITUTE OF CHILD HEALTH & HUMAN DEVELOPMENT · PI BONIFACINO, JUAN · 2009 to 2025
$48.3M
University of Pennsylvania Postdoctoral Opportunities in Research and TeachingK12GM081259 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI Janis K. Burkhardt · 2007 to 2026
$20.1M
TRAINING PROGRAM IN CELL AND MOLECULAR BIOLOGYT32GM007229 · NIGMS · UNIVERSITY OF PENNSYLVANIA · PI BARTOLOMEI, MARISA S. · 1985 to 2023
$14.0M
TRAINING GRANT IN HEMOSTASIS AND THROMBOSIST32HL007971 · NHLBI · UNIVERSITY OF PENNSYLVANIA · PI Rodney M Camire · 2001 to 2026
$10.6M
Hermansky Pudlak Syndrome &melanosome formationR01EY015625 · NEI · UNIVERSITY OF PENNSYLVANIA · PI Michael S Marks · 2004 to 2026
$9.2M
BLOC-1 and BLOC-2 function in melanosome maturationF32AR062476 · NIAMS · UNIVERSITY OF PENNSYLVANIA · PI DENNIS, MEGAN KATHLEEN · 2012 to 2014
$164k
Intramural NIH HHSNEI NIH HHS R01 EY015625NHLBI NIH HHS T32 HL007971NIAMS NIH HHS F32 AR062476NIGMS NIH HHS K12 GM081259NIGMS NIH HHS T32 GM007229Wellcome Trust 078327
6 · The paper itself

Abstract

Cell types that generate unique lysosome-related organelles (LROs), such as melanosomes in melanocytes, populate nascent LROs with cargoes that are diverted from endosomes. Cargo sorting toward melanosomes correlates with binding via cytoplasmically exposed sorting signals to either heterotetrameric adaptor AP-1 or AP-3. Some cargoes bind both adaptors, but the relative contribution of each adaptor to cargo recognition and their functional interactions with other effectors during transport to melanosomes are not clear. Here we exploit targeted mutagenesis of the acidic dileucine-based sorting signal in the pigment cell-specific protein OCA2 to dissect the relative roles of AP-1 and AP-3 in transport to melanosomes. We show that binding to AP-1 or AP-3 depends on the primary sequence of the signal and not its position within the cytoplasmic domain. Mutants that preferentially bound either AP-1 or AP-3 each trafficked toward melanosomes and functionally complemented OCA2 deficiency, but AP-3 binding was necessary for steady-state melanosome localization. Unlike tyrosinase, which also engages AP-3 for optimal melanosomal delivery, both AP-1- and AP-3-favoring OCA2 variants required BLOC-1 for melanosomal transport. These data provide evidence for distinct roles of AP-1 and AP-3 in OCA2 transport to melanosomes and indicate that BLOC-1 can cooperate with either adaptor during cargo sorting to LROs.

Indexed as

Adaptor Protein Complex 1Adaptor Protein Complex 3Amino Acid MotifsAmino Acid SequenceAmino Acid SubstitutionAnimalsCarrier ProteinsCell LineDipeptidesHumansIntracellular Signaling Peptides and ProteinsLectinsMelanocytesMelanosomesMembrane Transport ProteinsMiceAdaptor Protein Complex 1Adaptor Protein Complex 3Bloc1s6 protein, mouseCarrier ProteinsDipeptidesIntracellular Signaling Peptides and ProteinsLectinsleucylleucineMembrane Transport ProteinsOCA2 protein, humanProtein Sorting Signals

Identifiers

PMID22718909
PMCPMC3418312
OpenAlexW1973987332

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC-SA
Read underepoch 390

Registered trials

None linked

Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.