Commander Complex-A Multifaceted Operator in Intracellular Signaling and Cargo

Overview

Journal Cells

Publisher MDPI

Specialties Biochemistry
Biophysics
Cell Biology
Molecular Biology

Date 2021 Dec 24

PMID 34943955

Citations 7

Authors

Saara Laulumaa

Markku Varjosalo

Affiliations

Soon will be listed here.

Abstract

Commander complex is a 16-protein complex that plays multiple roles in various intracellular events in endosomal cargo and in the regulation of cell homeostasis, cell cycle and immune response. It consists of COMMD1-10, CCDC22, CCDC93, DENND10, VPS26C, VPS29, and VPS35L. These proteins are expressed ubiquitously in the human body, and they have been linked to diseases including Wilson's disease, atherosclerosis, and several types of cancer. In this review we describe the function of the commander complex in endosomal cargo and summarize the individual known roles of COMMD proteins in cell signaling and cancer. It becomes evident that commander complex might be a much more important player in intracellular regulation than we currently understand, and more systematic research on the role of commander complex is required.

Citing Articles

COMMD3 Regulates Copper Metabolism via the ATOX1-ATP7A-LOX Axis to Promote Multiple Myeloma Progression.

Wang Y, Zhang B, Fan F, Zhao F, Xu J, Zheng Y Biomedicines. 2025; 13(2).

PMID: 40002764 PMC: 11852399. DOI: 10.3390/biomedicines13020351.

EndoMAP.v1, a Structural Protein Complex Landscape of Human Endosomes.

Gonzalez-Lozano M, Schmid E, Whelan E, Jiang Y, Paulo J, Walter J bioRxiv. 2025; .

PMID: 39975243 PMC: 11839024. DOI: 10.1101/2025.02.07.636106.

Impairment of DET1 causes neurological defects and lethality in mice and humans.

Karayel O, Soung A, Gurung H, Schubert A, Klaeger S, Kschonsak M Proc Natl Acad Sci U S A. 2025; 122(7):e2422631122.

PMID: 39937864 PMC: 11848315. DOI: 10.1073/pnas.2422631122.

Monocytic Differentiation of Human Acute Myeloid Leukemia Cells: A Proteomic and Phosphoproteomic Comparison of FAB-M4/M5 Patients with and without Nucleophosmin 1 Mutations.

Selheim F, Aasebo E, Reikvam H, Bruserud O, Hernandez-Valladares M Int J Mol Sci. 2024; 25(10).

PMID: 38791118 PMC: 11121526. DOI: 10.3390/ijms25105080.

The commander complex is the Swiss Army knife of endosomal trafficking.

Leneva N, Kovtun O Nat Struct Mol Biol. 2024; 31(6):856-858.

PMID: 38783077 DOI: 10.1038/s41594-024-01326-2.

References

Riera-Romo M . COMMD1: A Multifunctional Regulatory Protein. J Cell Biochem. 2017; 119(1):34-51. DOI: 10.1002/jcb.26151. View

Wang J, Fedoseienko A, Chen B, Burstein E, Jia D, Billadeau D . Endosomal receptor trafficking: Retromer and beyond. Traffic. 2018; 19(8):578-590. PMC: 6043395. DOI: 10.1111/tra.12574. View

Harbour M, Breusegem S, Seaman M . Recruitment of the endosomal WASH complex is mediated by the extended 'tail' of Fam21 binding to the retromer protein Vps35. Biochem J. 2011; 442(1):209-20. DOI: 10.1042/BJ20111761. View

de Bie P, van de Sluis B, Burstein E, van de Berghe P, Muller P, Berger R . Distinct Wilson's disease mutations in ATP7B are associated with enhanced binding to COMMD1 and reduced stability of ATP7B. Gastroenterology. 2007; 133(4):1316-26. PMC: 2857755. DOI: 10.1053/j.gastro.2007.07.020. View

Li Y, Calvo S, Gutman R, Liu J, Mootha V . Expansion of biological pathways based on evolutionary inference. Cell. 2014; 158(1):213-25. PMC: 4171950. DOI: 10.1016/j.cell.2014.05.034. View

McNally K, Faulkner R, Steinberg F, Gallon M, Ghai R, Pim D . Retriever is a multiprotein complex for retromer-independent endosomal cargo recycling. Nat Cell Biol. 2017; 19(10):1214-1225. PMC: 5790113. DOI: 10.1038/ncb3610. View

Chen K, Healy M, Collins B . Towards a molecular understanding of endosomal trafficking by Retromer and Retriever. Traffic. 2019; 20(7):465-478. DOI: 10.1111/tra.12649. View

Zhang J, Zhang K, Qi L, Hu Q, Shen Z, Liu B . DENN domain-containing protein FAM45A regulates the homeostasis of late/multivesicular endosomes. Biochim Biophys Acta Mol Cell Res. 2019; 1866(5):916-929. DOI: 10.1016/j.bbamcr.2019.02.006. View

Tao T, Liu F, Klomp L, Wijmenga C, Gitlin J . The copper toxicosis gene product Murr1 directly interacts with the Wilson disease protein. J Biol Chem. 2003; 278(43):41593-6. DOI: 10.1074/jbc.C300391200. View

10.

Schou K, Andersen J, Pedersen L . A divergent calponin homology (NN-CH) domain defines a novel family: implications for evolution of ciliary IFT complex B proteins. Bioinformatics. 2013; 30(7):899-902. DOI: 10.1093/bioinformatics/btt661. View

11.

Hein M, Hubner N, Poser I, Cox J, Nagaraj N, Toyoda Y . A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell. 2015; 163(3):712-23. DOI: 10.1016/j.cell.2015.09.053. View

12.

Kendall A, Xie B, Xu P, Wang J, Burcham R, Frazier M . Mammalian Retromer Is an Adaptable Scaffold for Cargo Sorting from Endosomes. Structure. 2020; 28(4):393-405.e4. PMC: 7145723. DOI: 10.1016/j.str.2020.01.009. View

13.

Mirrashidi K, Elwell C, Verschueren E, Johnson J, Frando A, Von Dollen J . Global Mapping of the Inc-Human Interactome Reveals that Retromer Restricts Chlamydia Infection. Cell Host Microbe. 2015; 18(1):109-21. PMC: 4540348. DOI: 10.1016/j.chom.2015.06.004. View

14.

Mouhadeb O, Shlomo S, Cohen K, Farkash I, Gruber S, Maharshak N . Impaired COMMD10-Mediated Regulation of Ly6C Monocyte-Driven Inflammation Disrupts Gut Barrier Function. Front Immunol. 2018; 9:2623. PMC: 6246736. DOI: 10.3389/fimmu.2018.02623. View

15.

Li H, Koo Y, Mao X, Sifuentes-Dominguez L, Morris L, Jia D . Endosomal sorting of Notch receptors through COMMD9-dependent pathways modulates Notch signaling. J Cell Biol. 2015; 211(3):605-17. PMC: 4639872. DOI: 10.1083/jcb.201505108. View

16.

Yang S, Li X, Yang M, Ren X, Hu J, Zhu X . FMNL2 destabilises COMMD10 to activate NF-κB pathway in invasion and metastasis of colorectal cancer. Br J Cancer. 2017; 117(8):1164-1175. PMC: 5674093. DOI: 10.1038/bjc.2017.260. View

17.

Wang X, He S, Zheng X, Huang S, Chen H, Chen H . Transcriptional analysis of the expression, prognostic value and immune infiltration activities of the COMMD protein family in hepatocellular carcinoma. BMC Cancer. 2021; 21(1):1001. PMC: 8424899. DOI: 10.1186/s12885-021-08699-3. View

18.

Voineagu I, Huang L, Winden K, Lazaro M, Haan E, Nelson J . CCDC22: a novel candidate gene for syndromic X-linked intellectual disability. Mol Psychiatry. 2011; 17(1):4-7. PMC: 3586744. DOI: 10.1038/mp.2011.95. View

19.

Dey G, Jaimovich A, Collins S, Seki A, Meyer T . Systematic Discovery of Human Gene Function and Principles of Modular Organization through Phylogenetic Profiling. Cell Rep. 2015; 10(6):993-1006. PMC: 5016211. DOI: 10.1016/j.celrep.2015.01.025. View

20.

Bartuzi P, Billadeau D, Favier R, Rong S, Dekker D, Fedoseienko A . CCC- and WASH-mediated endosomal sorting of LDLR is required for normal clearance of circulating LDL. Nat Commun. 2016; 7:10961. PMC: 4792963. DOI: 10.1038/ncomms10961. View