title: Complement inhibitor CD55 governs the integrity of membrane rafts in pancreatic beta cells, but plays no role in insulin secretion.
abstract: CD55 is a glycosylphosphatidylinositol-anchored protein, which inhibits complement activation by acting on the complement C3 convertases. CD55 is widely localized in the cholesterol rich regions of the cell plasma membrane termed membrane rafts. CD55 is attached to these specialized regions via a GPI link on the outer leaflet of the plasma membrane. Membrane rafts anchor many important signaling proteins, which control several cellular functions within the cell. For example, we recently demonstrated that the membrane raft protein and complement inhibitor CD59 also controls insulin secretion by an intracellular mechanism. Therefore, we have in this study aimed at addressing the expression and function of CD55 in pancreatic beta cells. To this end, we observe that CD55 is highly expressed in INS1 832/13 beta cells as well as human pancreatic islets. Diabetic human islets show a tendency for increased expression of CD55 when compared to the healthy controls. Importantly, silencing of CD55 in INS1 832/13 cells does not affect their insulin secretory capacity. On the other hand, silencing of CD55 diminished the intensity of membrane rafts as determined by Atto-SM staining. We hence conclude that CD55 expression is affected by glycemic status in human islets and plays a critical role in maintaining the conserved structure of rafts in pancreatic islets, which is similar to that of the related complement inhibitor CD59. However CD55 does not interfere with insulin secretion in beta cells, which is in sharp contrast to the action of the complement inhibitor CD59.
authors: Department of Clinical Sciences, Lund University, SE 20502 Malmö, Sweden.
authors: Vini
authors: V
authors: Nagaraj
authors: Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE 20502 Malmö, Sweden.
authors: Ben
authors: B
authors: King
authors: Department of Clinical Sciences, Lund University, SE 20502 Malmö, Sweden.
authors: Petter
authors: P
authors: Storm
authors: Department of Clinical Sciences, Lund University, SE 20502 Malmö, Sweden.
authors: Petter
authors: P
authors: Vikman
authors: Department of Clinical Sciences, Lund University, SE 20502 Malmö, Sweden.
authors: Emilia
authors: E
authors: Ottosson-Laakso
authors: Medical Protein Chemistry, Department of Translational Medicine, Lund University, SE 20502 Malmö, Sweden.
authors: Anna M
authors: AM
authors: Blom
authors: Department of Clinical Sciences, Lund University, SE 20502 Malmö, Sweden. Electronic address: erik.renstrom@med.lu.se.
authors: Erik
authors: E
authors: Renström
mesh_terms: D000818:Animals; D018958:CD55 Antigens / Q000235:genetics / Q000502:physiology*; D002460:Cell Line; D020869:Gene Expression Profiling; D006801:Humans; D007328:Insulin / Q000378:metabolism*; D000078790:Insulin Secretion; D007515:Islets of Langerhans / Q000378:metabolism*; D021962:Membrane Microdomains / Q000378:metabolism*; D051381:Rats
chemical_list: D018958:CD55 Antigens; D007328:Insulin
keywords: CD55; Complement inhibitors; Insulin secretion; Membrane rafts