GDP-fucose transporter 1 (SLC35C1) (SLC35C1)

GDP-fucose transporter 1 (SLC35C1) is a multi-pass transmembrane protein located in the Golgi apparatus that facilitates the transport of GDP-fucose from the cytosol into the Golgi lumen (UniProt: Q96A29). This transport is a critical step in the fucosylation of proteins and lipids, which is essential for the synthesis of functional glycans such as the sialyl-Lewis X epitope on leukocytes (PubMed: 11433324). These glycans are necessary for leukocyte tethering and rolling on the vascular endothelium during the inflammatory response. Mutations in the SLC35C1 gene lead to Leukocyte Adhesion Deficiency Type II (LAD II), also known as Congenital Disorder of Glycosylation type IIc (CDG-IIc), a rare primary immunodeficiency characterized by recurrent infections, persistent leukocytosis, and severe growth and mental retardation (PubMed: 11175295). In some patients, oral L-fucose supplementation can partially restore fucosylation by utilizing a salvage pathway to bypass the transporter defect (PubMed: 11331641). Additionally, SLC35C1 is of interest in oncology because aberrant fucosylation is frequently associated with tumor progression, immune evasion, and metastasis (PubMed: 28651079).

Other names

Solute carrier family 35 member C1FUCT1GDP-L-fucose transporter 1CDG2CSialic acid transporter-like 2

The primary therapeutic mechanism involves substrate supplementation with L-fucose, which increases the intracellular pool of fucose and allows for the restoration of Golgi fucosylation through an alternative salvage pathway, thereby bypassing the defective SLC35C1 transporter in certain patients (PubMed: 11331641).