Protein_Domain

Part:BBa_K4040000

Designed by: Mengmei Zhu   Group: iGEM21_NMU_China   (2021-09-01)
Revision as of 07:08, 4 October 2021 by Ytong (Talk | contribs)


Intracellular Domain of the MEGF10 Protein

Sequence and Features


Assembly Compatibility:
  • 10
    COMPATIBLE WITH RFC[10]
  • 12
    COMPATIBLE WITH RFC[12]
  • 21
    COMPATIBLE WITH RFC[21]
  • 23
    COMPATIBLE WITH RFC[23]
  • 25
    COMPATIBLE WITH RFC[25]
  • 1000
    INCOMPATIBLE WITH RFC[1000]
    Illegal SapI.rc site found at 519

Usage and Biology

MEGF10 is a membrane receptor involved in phagocytosis by macrophages and astrocytes of apoptotic cells. Receptor for C1q, an eat-me signal, that binds phosphatidylserine expressed on the surface of apoptotic cells.[1]It cooperates with ABCA1 within the process of engulfment. Promotes the formation of large intracellular vacuoles and may be responsible for the uptake of amyloid-beta peptides.[2]and is necessary for astrocyte-dependent apoptotic neuron clearance in the developing cerebellum.[3]MEGF10 plays role in muscle cell proliferation, adhesion and motility. Is also an essential factor in the regulation of myogenesis. Controls the balance between skeletal muscle satellite cells proliferation and differentiation through regulation of the notch signaling pathway.[4]It may also function in the mosaic spacing of specific neuron subtypes in the retina through homotypic retinal neuron repulsion. Mosaics provide a mechanism to distribute each cell type evenly across the retina, ensuring that all parts of the visual field have access to a full set of processing elements.[5-10]

Figure 1. Structure of MEGF10.

Background and detail description

Used for a CAR

The synthetic receptors were constructed to contain an scFv derived from an antibody recognizing the virus spike protein, CR3022, which has been reported to bind with the receptor-binding domain of the SARS-CoV-2 S glycoprotein with high affinity, and the CD8 transmembrane domain present in the aCD19 CAR for T cells. For the cytoplasmic domains, we used the common g subunit of Fc receptors (CARg), MEGF10 (CARMEGF10), MERTK(CARMERTK) and CD3z (CARz) in our study.

These cytoplasmic domains are capable of promoting phagocytosis by macrophages.More details and experimental results can be found in CAR-MEGF10(BBa_K4040015).

References

[1]Iram T, Ramirez-Ortiz Z, Byrne MH, Coleman UA, Kingery ND, Means TK, Frenkel D, El Khoury J. Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes.JNeurosci.2016 May 11;36(19):5185-92. doi: 10.1523/JNEUROSCI.3850-15.2016. PMID: 27170117; PMCID: PMC4863057.

[2]Singh TD, Park SY, Bae JS, Yun Y, Bae YC, Park RW, Kim IS. MEGF10 functions as a receptor for the uptake of amyloid-β. FEBS Lett. 2010 Sep 24;584(18):3936-42. doi: 10.1016/j.febslet.2010.08.050. Epub 2010 Sep 7. PMID: 20828568.

[3]Suzuki E, Nakayama M. MEGF10 is a mammalian ortholog of CED-1 that interacts with clathrin assembly protein complex 2 medium chain and induces large vacuole formation. Exp Cell Res. 2007 Oct 15;313(17):3729-42. doi: 10.1016/j.yexcr.2007.06.015. Epub 2007 Jul 3. PMID: 17643423.

[4]Iram T, Ramirez-Ortiz Z, Byrne MH, Coleman UA, Kingery ND, Means TK, Frenkel D, El Khoury J. Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes. J Neurosci. 2016 May 11;36(19):5185-92. doi: 10.1523/JNEUROSCI.3850-15.2016. PMID: 27170117; PMCID: PMC4863057.

[5]Suzuki E, Nakayama M. The mammalian Ced-1 ortholog MEGF10/KIAA1780 displays a novel adhesion pattern. Exp Cell Res. 2007 Jul 1;313(11):2451-64. doi: 10.1016/j.yexcr.2007.03.041. Epub 2007 Apr 19. PMID: 17498693.

[6]Suzuki E, Nakayama M. MEGF10 is a mammalian ortholog of CED-1 that interacts with clathrin assembly protein complex 2 medium chain and induces large vacuole formation. Exp Cell Res. 2007 Oct 15;313(17):3729-42. doi: 10.1016/j.yexcr.2007.06.015. Epub 2007 Jul 3. PMID: 17643423.

[7]Singh TD, Park SY, Bae JS, Yun Y, Bae YC, Park RW, Kim IS. MEGF10 functions as a receptor for the uptake of amyloid-β. FEBS Lett. 2010 Sep 24;584(18):3936-42. doi: 10.1016/j.febslet.2010.08.050. Epub 2010 Sep 7. PMID: 20828568.

[8]Logan CV, Lucke B, Pottinger C, Abdelhamed ZA, Parry DA, Szymanska K, Diggle CP, van Riesen A, Morgan JE, Markham G, Ellis I, Manzur AY, Markham AF, Shires M, Helliwell T, Scoto M, Hübner C, Bonthron DT, Taylor GR, Sheridan E, Muntoni F, Carr IM, Schuelke M, Johnson CA. Mutations in MEGF10, a regulator of satellite cell myogenesis, cause early onset myopathy, areflexia, respiratory distress and dysphagia (EMARDD). Nat Genet. 2011 Nov 20;43(12):1189-92. doi: 10.1038/ng.995. PMID: 22101682.

[9]Iram T, Ramirez-Ortiz Z, Byrne MH, Coleman UA, Kingery ND, Means TK, Frenkel D, El Khoury J. Megf10 Is a Receptor for C1Q That Mediates Clearance of Apoptotic Cells by Astrocytes. J Neurosci. 2016 May 11;36(19):5185-92. doi: 10.1523/JNEUROSCI.3850-15.2016. PMID: 27170117; PMCID: PMC4863057.

[10]Saha M, Mitsuhashi S, Jones MD, Manko K, Reddy HM, Bruels CC, Cho KA, Pacak CA, Draper I, Kang PB. Consequences of MEGF10 deficiency on myoblast function and Notch1 interactions. Hum Mol Genet. 2017 Aug 1;26(15):2984-3000. doi: 10.1093/hmg/ddx189. PMID: 28498977; PMCID: PMC6075367.


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