title: Leukocyte adhesion deficiency II patients with a dual defect of the GDP-fucose transporter.
abstract: Leukocyte adhesion deficiency II (LAD II) is a rare congenital disease caused by defective fucosylation leading to immuno-deficiency and psychomotor retardation. We have previously identified the genetic defect of LAD II in a patient whose Golgi GDP-fucose transporter (GFTP) bears a single amino acid exchange that renders this protein nonfunctional but correctly localized to the Golgi. We now report a novel dual defect by which a truncated GFTP causes the disease in a new LAD II patient. We show that the truncation renders this GFTP unable to localize to the Golgi, the compartment where it is required. Furthermore, the missing part of the GFTP can be dissected into 2 regions, one that is needed for Golgi localization and one that is additionally required for the function of the GFTP. We investigated the subcellular localization of all known defective GFTPs allowing us to divide all genetically analyzed LAD II patients into 2 groups, one in which single amino acid exchanges in the GFTP impair its function but not its subcellular localization, and another group with a dual defect in function and Golgi expression of the GFTP due to the absence of 2 important molecular regions.
authors.affiliation: Max Planck Institute of Molecular Biomedicine and Institute of Cell Biology, ZMBE, University of Münster, Von-Esmarch-Strasse 56, 48149 Münster, Germany.
authors.forename: Yvonne
authors.initials: Y
authors.lastname: Helmus
authors.forename: Jonas
authors.initials: J
authors.lastname: Denecke
authors.forename: Sviatlana
authors.initials: S
authors.lastname: Yakubenia
authors.forename: Peter
authors.initials: P
authors.lastname: Robinson
authors.forename: Kerstin
authors.initials: K
authors.lastname: Lühn
authors.forename: Diana L
authors.initials: DL
authors.lastname: Watson
authors.forename: Paraic J
authors.initials: PJ
authors.lastname: McGrogan
authors.forename: Dietmar
authors.initials: D
authors.lastname: Vestweber
authors.forename: Thorsten
authors.initials: T
authors.lastname: Marquardt
authors.forename: Martin K
authors.initials: MK
authors.lastname: Wild
mesh_terms: D001483:Base Sequence; D003001:Cloning, Molecular; D017931:DNA Primers; D005260:Female; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D005643:Fucose / Q000494:pharmacology; D006801:Humans; D007223:Infant; D018370:Leukocyte-Adhesion Deficiency Syndrome / Q000235:genetics*; D009004:Monosaccharide Transport Proteins / Q000737:chemistry / Q000235:genetics*; D009504:Neutrophils / Q000502:physiology; D011487:Protein Conformation
chemical_list: D017931:DNA Primers; D009004:Monosaccharide Transport Proteins; C426650:SLC35C1 protein, human; D005643:Fucose