N-Glycosylation of extracellular matrix protein 1 (ECM1) regulates its secretion, which is unrelated to lipoid proteinosis.
Extracellular matrix protein 1 (ECM1) is expressed in a wide variety of tissues and plays important roles in extracellular matrix formation. Additionally, ECM1 gene mutations cause lipoid proteinosis (LP), a rare skin condition of genetic origin. However, an effective therapeutic approach of LP is not established. Here, we showed that ECM1 gene mutation observed in LP patients significantly suppresses its secretion. As ECM1 has three putative N-glycosylation sites and most of mutated ECM1 observed in LP patients are defective in these N-glycosylation sites, we investigated the correlation between LP and N-glycosylation of ECM1. We identified that the Asn(354) and Asn(444) residues in ECM1 were N-glycosylated by mass spectrometry analysis. In addition, an N-linked glycan at Asn(354) negatively regulated secretion of ECM1, contrary to LP patient-derived mutants. These results indicate that the defect of N-glycosylation in ECM1 is not involved in the aberration of secretion of LP-derived mutated ECM1.
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Shiho
S
Uematsu
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Yuki
Y
Goto
Global Research Cluster, RIKEN, Wako 351-0198, Japan.
Takehiro
T
Suzuki
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Yukiko
Y
Sasazawa
Global Research Cluster, RIKEN, Wako 351-0198, Japan.
Naoshi
N
Dohmae
Department of Applied Chemistry, Faculty of Science and Technology, Keio University, Yokohama 223-8522, Japan.
Siro
S
Simizu
CBB, Coomassie Brilliant Blue; ECM1, extracellular matrix protein 1; ER, endoplasmic reticulum; Extracellular matrix protein 1; LP, lipoid proteinosis; Lipoid proteinosis; MALDI-TOF MS, matrix-assisted laser desorption time flight mass spectrometry; N-Glycosylation; PBS, phosphate-buffered saline; PNGase F, peptide N-glycosidase F; SDS, sodium dodecyl sulfate; Secretion