Tuning the Functionality by Splicing: Factor H and Its Alternative Splice Variant FHL-1 Share a Gene but Not All Functions
Schmidt, Christoph Q.
Frontiers in Immunology ; 11 (2020). - Art.-Nr. 596415. - ISSN 1664-3224. - eISSN 1664-3224
Link to original publicationhttps://dx.doi.org/10.3389/fimmu.2020.596415
InstitutionsUKU. Institut für Naturheilkunde und Klinische Pharmakologie
UKU. Institut für Klinische und Experimentelle Trauma-Immunologie
The alternative pathway regulator Factor H-like protein 1 (FHL-1) is composed of the first 7 N-terminal complement control protein domains of Factor H (FH) and protects host surfaces from uncontrolled complement attack. Although FHL-1 shares the N-terminal regulatory domains with FH, it was thought to be a weaker regulator. Recently, the regulatory activity of FHL-1 was shown to be comparable to FH. Nonetheless, the question remained whether FHL-1 is an indispensable, unique regulator. The discovery that FHL-1 is the predominant regulator on Bruch’s membrane, a critical site for the onset and progression of age-related-macular degeneration (AMD), showed that FHL-1 is essential for complement regulation. A common single nucleotide polymorphism in FH/FHL-1 that predisposes for AMD underlines the important role of FHL-1 in this context. Reports that some cancer tissues specifically upregulate FHL-1 expression, thereby evading immune surveillance, suggests a pronounced regulatory activity of the splice variant. Several microorganisms specifically recruit FHL-1 to evade complement attack. From a phylogenetic point of view, FHL-1 appears much later than other complement regulators, which could imply a specific role that is possibly not systemic but rather tissue specific. This review focuses on the current knowledge of FHL-1 and its physiological and pathophysiological roles.
Fachliche Einordnung[GND]: Faktor H, Cytoprotektion, Heparansulfat
[MeSH]: C-reactive protein, Cytoprotection, Complement factor H, Bruch membrane, Macular degeneration, Heparitin sulfate
[Freie Tags]: Factor H-like protein 1, cell protection, complement system, regulatory selectivity, REGULATORS FACTOR-H, BRUCHS MEMBRANE IMPLICATIONS, NONSELF DISCRIMINATION, TREPONEMA-DENTICOLA, HEPARAN-SULFATE, BINDING, DISEASE
DDC 610 / Medicine & health
LicenseCC BY 4.0 International
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DOI & citation
Please use this identifier to cite or link to this item: http://dx.doi.org/10.18725/OPARU-37049