Dataset Information

Human O-Mannosylation independent of POMT1/2

ABSTRACT: Protein O-mannosylation is found in yeast and metazoans and a family of conserved orthologous polypeptide O-mannosyltransferases is believed to initiate this important posttranslational modification. We recently discovered that the large families of cadherins and protocadherins carry highly conserved O-Man glycans in specific EC domains, and it was suggested that the function of E-Cadherin was dependent on the O-Man glycans. Deficiencies in the two human polypeptide O-mannosyltransferases, POMT1 and T2, underlie a subgroup of congenital muscular dystrophies (CMD) designated α-dystroglycanopathies, because deficient O-Man glycans on -dystroglycan impair laminin interaction with -dystroglycan and the dystrophin complex. In order to explore the functions of O-Man glycans on cadherins and protocadherins we used a combinatorial gene editing strategy in multiple cell lines to evaluate to the role of the two POMTs initiation O-Man glycosylation and the major enzyme elongating O-Man glycans, the POMGNT1 2GlcNAc-transferase. Surprisingly, we discovered that O-Man glycans on cadherins and protocadherins do not appear to require POMT1 and T2 and moreover that the O-Man glycans on these proteins are not elongated in contrast to those on dystroglycan.

INSTRUMENT(S): Orbitrap Fusion ETD, LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Kidney

SUBMITTER: Adnan Halim

LAB HEAD: Henrik Clausen

PROVIDER: PXD004358 | Pride | 2017-05-18

REPOSITORIES: Pride

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Dataset's files

Source:

			Action	DRS
	141010_VelosLC1_Ida_HekSC_POMGNT1_KO_PNGaseF_LWAC_90_2h_HCD_ETD_ConA_1.raw	Raw
	141010_VelosLC1_Ida_HekSC_POMGNT1_KO_PNGaseF_LWAC_90_2h_HCD_ETD_ConA_1_2.msf	Msf
	141010_VelosLC1_Ida_HekSC_POMGNT1_KO_PNGaseF_LWAC_90_2h_HCD_ETD_ConA_2.raw	Raw
	150602_Velos_LC1_Ida_HEK293_Cosmc_POMGnT1_POMT1_KO_ConAMay2015_4xHex.msf	Msf
	150602_Velos_LC1_Ida_HEK293_Cosmc_POMGnT1_POMT1_KO_ConAMay2015_5HCD_5ETD_LWAC22.raw	Raw

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Publications

Mammalian O-mannosylation of cadherins and plexins is independent of protein O-mannosyltransferases 1 and 2.

Larsen Ida Signe Bohse ISB Narimatsu Yoshiki Y Joshi Hiren Jitendra HJ Yang Zhang Z Harrison Oliver J OJ Brasch Julia J Shapiro Lawrence L Honig Barry B Vakhrushev Sergey Y SY Clausen Henrik H Halim Adnan A

The Journal of biological chemistry 20170516 27

Protein O-mannosylation is found in yeast and metazoans, and a family of conserved orthologous protein O-mannosyltransferases is believed to initiate this important post-translational modification. We recently discovered that the cadherin superfamily carries O-linked mannose (O-Man) glycans at highly conserved residues in specific extracellular cadherin domains, and it was suggested that the function of E-cadherin was dependent on the O-Man glycans. Deficiencie ...[more]

PMID: 28512129

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Project description:The majority of cell surface and secreted proteins are modified by glycans and this glycosylation process plays an important role in the development of multicellular organisms. These glycan modifications enable communication between cells and the extracellular matrix via interactions with specific glycan-binding lectins and the regulation of receptor-mediated signalling. Glycosylation plays an important role in myogenesis and the development of muscle tissue but our molecular understanding of the precise glycans, catalytic enzymes and lectins involved remain only partially understood. Here, we quantified dynamic remodeling of the membrane-associated proteome during in vitro myogenesis. We observed wide-spread changes in the abundance of several receptors and important enzymes regulating glycosylation. Quantification of released N-linked glycans via glycomic analysis confirmed remodeling of the glycome with a switch in sialic acid linkages, and changes in di-galactosylation and paucimannosylation. Quantitative glycoproteomic analysis with stable isotope labelling, enrichment of glycopeptides and analysis via multiple fragmentation approaches identified precise glycoproteins containing these regulated glycans including integrins and growth factor receptors. Myogenesis was also associated with the regulation of several lectins including the up-regulation of Galectin-1 (LGALS1). CRISPR/Cas9-mediated deletion of Lgals1 inhibited differentiation and myotube formation suggesting an early defect in the myogenic program. We also observed similar changes in N-glycosylation and the up-regulation of LGALS1 during postnatal skeletal muscle development in mice. Finally, treatment of new-born mice with recombinant adeno-associated viruses to express LGALS1 in the musculature resulted in enhanced muscle mass. Our data will be a valuable resource to further understand the role of glycosylation and lectins on myogenesis and may aid in the development of intervention strategies aimed at promoting healthy muscle.

Dataset Information

Human O-Mannosylation independent of POMT1/2

Dataset's files

Publications

Mammalian <i>O</i>-mannosylation of cadherins and plexins is independent of protein <i>O</i>-mannosyltransferases 1 and 2.

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