C-mannosylation regulates stabilization of RAMP1 protein and RAMP1-mediated cell migration

Hayato Mizuta, Ayane Takakusaki, Takehiro Suzuki, Keisuke Otake, Naoshi Dohmae, Siro Simizu

Research output: Contribution to journalArticlepeer-review

2 Citations (Scopus)


C-mannosylation is a unique type of protein glycosylation via C-C linkage between an α-mannose and a tryptophan residue. This modification has been identified in about 30 proteins and regulates several functions, such as protein secretion and intracellular localization, as well as protein stability. About half of C-mannosylated proteins are categorized as proteins containing thrombospondin type 1 repeat domain or type I cytokine receptors. To evaluate whether C-mannosylation broadly affects protein functions regardless of protein domain or family, we have sought to identify other types of C-mannosylated protein and analyse their functions. In this study, we focused on receptor activity modifying protein 1, which neither contains thrombospondin type 1 repeat domain nor belongs to the type I cytokine receptors. Our mass spectrometry analysis demonstrated that RAMP1 is C-mannosylated at Trp56. It has been shown that RAMP1 transports to the plasma membrane after dimerization with calcitonin receptor-like receptor and is important for ligand-dependent downstream signalling activation. Our results showed that C-mannosylation has no effect on this transport activity. On the other hand, C-mannosylation did enhance protein stability and cell migration activity. Our data may provide new insight into both C-mannosylation research and novel RAMP1 analysis.

Original languageEnglish
Pages (from-to)196-208
Number of pages13
JournalFEBS Journal
Issue number1
Publication statusPublished - 2023 Jan


  • C-mannosylation
  • CLR
  • RAMP1
  • migration
  • stability

ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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