Ephrin

Function

Ephrins (Eph) are the membrane-bound ligands of ephrin receptors. The binding of Eph and ephrin receptors is achieved via cell-cell interaction. Eph/Eph receptor signaling regulates embryonic development, guidance of axon growth, long-term potentiation, angiogenesis and stem-cell differentiation ^[1]. See also Ephrin receptor, Eph/ephrin signaling pathway, Ephrin Type-A Receptor.

Ephrin-A3 has a role in forming precise tonotropy in the auditory brainstem to ensure accurate sound discrimination^[2].
Ephrin-A5 is required for the proper guidance and mapping of retinal axons in the mammalian midbrain^[3].
Ephrin-B1 has a role in palatal shelf outgrowth^[4].
Ephrin-B2 is a regulator of VEGFR signalling and thus controls angiogenic growth^[5].
Ephrin-B3 plays a key role at the midline to regulate axonal crossing^[6].

Disease

Eph-A5 is implicated in spinal cord injury. Eph-A1 is implicated in myocardial injury and renal reperfusion injury.

Structural highlights

(PDB code 3mx0).^[7]

Structure of glycosylated human ephrin-A5 receptor-binding domain (green) complex with ephrin type A receptor 2 (cyan) (PDB code 3mx0).

Drag the structure with the mouse to rotate

3D structures of ephrin3D structures of ephrin

Updated on 18-June-2024

ReferencesReferences

↑ Egea J, Klein R. Bidirectional Eph-ephrin signaling during axon guidance. Trends Cell Biol. 2007 May;17(5):230-8. Epub 2007 Apr 8. PMID:17420126 doi:http://dx.doi.org/10.1016/j.tcb.2007.03.004
↑ Hoshino N, Altarshan Y, Alzein A, Fernando AM, Nguyen HT, Majewski EF, Chen VC, Rochlin MW, Yu WM. Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem. J Comp Neurol. 2021 Nov;529(16):3633-3654. PMID:34235739 doi:10.1002/cne.25213
↑ Frisén J, Yates PA, McLaughlin T, Friedman GC, O'Leary DD, Barbacid M. Ephrin-A5 (AL-1/RAGS) is essential for proper retinal axon guidance and topographic mapping in the mammalian visual system. Neuron. 1998 Feb;20(2):235-43. PMID:9491985 doi:10.1016/s0896-6273(00)80452-3
↑ Bush JO, Soriano P. Ephrin-B1 forward signaling regulates craniofacial morphogenesis by controlling cell proliferation across Eph-ephrin boundaries. Genes Dev. 2010 Sep 15;24(18):2068-80. PMID:20844017 doi:10.1101/gad.1963210
↑ Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Luthi U, Barberis A, Benjamin LE, Makinen T, Nobes CD, Adams RH. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 2010 May 27;465(7297):483-6. doi: 10.1038/nature09002. PMID:20445537 doi:10.1038/nature09002
↑ Kullander K, Croll SD, Zimmer M, Pan L, McClain J, Hughes V, Zabski S, DeChiara TM, Klein R, Yancopoulos GD, Gale NW. Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control. Genes Dev. 2001 Apr 1;15(7):877-88. PMID:11297511 doi:10.1101/gad.868901
↑ Himanen JP, Yermekbayeva L, Janes PW, Walker JR, Xu K, Atapattu L, Rajashankar KR, Mensinga A, Lackmann M, Nikolov DB, Dhe-Paganon S. Architecture of Eph receptor clusters. Proc Natl Acad Sci U S A. 2010 May 26. PMID:20505120

Proteopedia Page Contributors and Editors (what is this?)Proteopedia Page Contributors and Editors (what is this?)

Michal Harel, Alexander Berchansky, Joel L. Sussman

[1] Egea J, Klein R. Bidirectional Eph-ephrin signaling during axon guidance. Trends Cell Biol. 2007 May;17(5):230-8. Epub 2007 Apr 8. PMID:17420126 doi:http://dx.doi.org/10.1016/j.tcb.2007.03.004

[2] Hoshino N, Altarshan Y, Alzein A, Fernando AM, Nguyen HT, Majewski EF, Chen VC, Rochlin MW, Yu WM. Ephrin-A3 is required for tonotopic map precision and auditory functions in the mouse auditory brainstem. J Comp Neurol. 2021 Nov;529(16):3633-3654. PMID:34235739 doi:10.1002/cne.25213

[3] Frisén J, Yates PA, McLaughlin T, Friedman GC, O'Leary DD, Barbacid M. Ephrin-A5 (AL-1/RAGS) is essential for proper retinal axon guidance and topographic mapping in the mammalian visual system. Neuron. 1998 Feb;20(2):235-43. PMID:9491985 doi:10.1016/s0896-6273(00)80452-3

[4] Bush JO, Soriano P. Ephrin-B1 forward signaling regulates craniofacial morphogenesis by controlling cell proliferation across Eph-ephrin boundaries. Genes Dev. 2010 Sep 15;24(18):2068-80. PMID:20844017 doi:10.1101/gad.1963210

[5] Wang Y, Nakayama M, Pitulescu ME, Schmidt TS, Bochenek ML, Sakakibara A, Adams S, Davy A, Deutsch U, Luthi U, Barberis A, Benjamin LE, Makinen T, Nobes CD, Adams RH. Ephrin-B2 controls VEGF-induced angiogenesis and lymphangiogenesis. Nature. 2010 May 27;465(7297):483-6. doi: 10.1038/nature09002. PMID:20445537 doi:10.1038/nature09002

[6] Kullander K, Croll SD, Zimmer M, Pan L, McClain J, Hughes V, Zabski S, DeChiara TM, Klein R, Yancopoulos GD, Gale NW. Ephrin-B3 is the midline barrier that prevents corticospinal tract axons from recrossing, allowing for unilateral motor control. Genes Dev. 2001 Apr 1;15(7):877-88. PMID:11297511 doi:10.1101/gad.868901

[7] Himanen JP, Yermekbayeva L, Janes PW, Walker JR, Xu K, Atapattu L, Rajashankar KR, Mensinga A, Lackmann M, Nikolov DB, Dhe-Paganon S. Architecture of Eph receptor clusters. Proc Natl Acad Sci U S A. 2010 May 26. PMID:20505120

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