Once a mammalian central nervous system axon is severed, it never regenerates. As a result, the neural circuit carried by this axon is permanently disrupted, and the dysfunction of that circuit remains a serious sequela for life. This is because chondroitin sulfate produced by glial scars caused by central nervous system injury functions as a potent axonal regeneration inhibitor. Although chondroitin sulfate induces an abnormal structure called dystrophic endball at the tip of axon via the neural cell receptor PTPRσ and inhibits its elongation, its detailed mechanism of operation has been unknown. In this review, we would like to outline the mechanism of axon regeneration inhibition by chondroitin sulfate, which was recently clarified by the authors.

N-glycan plays a pivotal role in the protein quality control system in the endoplasmic reticulum (ER). Lectin chaperones recognize monoglucosylated glycoproteins to promote their folding. If glycoproteins cannot attain their tertiary structure, mannoses of their N-glycans are trimmed to be recognized by lectin components for degradation. Then, such misfolded glycoproteins are retrotranslocated to the cytosol, where they are degraded by proteasomes. This fundamental machinery is conserved from yeast to mammals, but it becomes more sophisticated through evolution because of multiplied and diverged genes in mammals. In this minireview, I would like to summarize the history and latest research of the N-glycan-dependent quality control system in the ER, especially focusing on the molecular mechanism of mannose trimming and lectin components for destruction in yeast and mammals.

N-Glycans, which are post-translational glycosylation modifications on asparagine, have diverse structures, and their functions vary based on their structures. Recent advances in the chemical, enzymatic, and chemoenzymatic synthesis and isolation of N-glycans have made it possible to produce high quantities of various N-glycans. These N-glycans have been widely used in chemical biology studies on elucidating their functions. Interaction analyses between lectins and various N-glycans have revealed the molecular basis of the recognition of N-glycans. In addition, proteins modified with chemically synthesized homogeneous N-glycans revealed the effects of N-glycan modification on protein function. Furthermore, the applications of N-glycans in drug development have been explored. This review introduces the recent advances in the chemical biology study on N-glycans.

The core α1,6-fucose structure, a major structure in asparagine-linked oligosaccharides, has a variety of biological and physiological characteristics. In eukaryotes, the core α1,6-fucose structure is biosynthesized by the α1,6-fucosyltransferase, FUT8. FUT8 is composed of a catalytic domain and two additional domains, an N-terminal α-helical (coiled-coil) and a C-terminal Src homology 3 (SH3) domain. The most recent structural and biochemical studies clearly show that these domains have precise functions. In this minireview, we summarize our current knowledge of the roles of the α-helical (coiled-coil) and SH3 domains in FUT8 functions, with a particular focus on the dimer formation that is essential for the activity, substrate recognition and other characteristics of this enzyme.

Once a mammalian central nervous system axon is severed, it never regenerates. As a result, the neural circuit carried by this axon is permanently disrupted, and the dysfunction of that circuit remains a serious sequela for life. This is because chondroitin sulfate produced by glial scars caused by central nervous system injury functions as a potent axonal regeneration inhibitor. Although chondroitin sulfate induces an abnormal structure called dystrophic endball at the tip of axon via the neural cell receptor PTPRσ and inhibits its elongation, its detailed mechanism of operation has been unknown. In this review, we would like to outline the mechanism of axon regeneration inhibition by chondroitin sulfate, which was recently clarified by the authors.

N-glycan plays a pivotal role in the protein quality control system in the endoplasmic reticulum (ER). Lectin chaperones recognize monoglucosylated glycoproteins to promote their folding. If glycoproteins cannot attain their tertiary structure, mannoses of their N-glycans are trimmed to be recognized by lectin components for degradation. Then, such misfolded glycoproteins are retrotranslocated to the cytosol, where they are degraded by proteasomes. This fundamental machinery is conserved from yeast to mammals, but it becomes more sophisticated through evolution because of multiplied and diverged genes in mammals. In this minireview, I would like to summarize the history and latest research of the N-glycan-dependent quality control system in the ER, especially focusing on the molecular mechanism of mannose trimming and lectin components for destruction in yeast and mammals.

N-Glycans, which are post-translational glycosylation modifications on asparagine, have diverse structures, and their functions vary based on their structures. Recent advances in the chemical, enzymatic, and chemoenzymatic synthesis and isolation of N-glycans have made it possible to produce high quantities of various N-glycans. These N-glycans have been widely used in chemical biology studies on elucidating their functions. Interaction analyses between lectins and various N-glycans have revealed the molecular basis of the recognition of N-glycans. In addition, proteins modified with chemically synthesized homogeneous N-glycans revealed the effects of N-glycan modification on protein function. Furthermore, the applications of N-glycans in drug development have been explored. This review introduces the recent advances in the chemical biology study on N-glycans.

The core α1,6-fucose structure, a major structure in asparagine-linked oligosaccharides, has a variety of biological and physiological characteristics. In eukaryotes, the core α1,6-fucose structure is biosynthesized by the α1,6-fucosyltransferase, FUT8. FUT8 is composed of a catalytic domain and two additional domains, an N-terminal α-helical (coiled-coil) and a C-terminal Src homology 3 (SH3) domain. The most recent structural and biochemical studies clearly show that these domains have precise functions. In this minireview, we summarize our current knowledge of the roles of the α-helical (coiled-coil) and SH3 domains in FUT8 functions, with a particular focus on the dimer formation that is essential for the activity, substrate recognition and other characteristics of this enzyme.