The HNK-1 Carbohydrate Epitope in the Eye: Basic Science and Functional Implications

Uusitalo, Marita; Kivelä, Tero

doi:10.1016/s1350-9462(00)00018-5

Cited by 19 publications

(25 citation statements)

References 173 publications

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“…Glycosyltransferases, which transfer monosaccharide units to an acceptor molecule, are responsible for the synthesis of carbohydrate moieties on proteins. The carbohydrate epitope Human Natural Killer 1 (HNK-1), found on several cell adhesion molecules such as the neural cell adhesion molecule (NCAM; [20]), is spatially and temporally regulated during development of the central and peripheral nervous systems. HNK-1 is assumed to be involved in cell-cell interactions such as cell adhesion [21], migration [22] and neurite extension [23].…”

Section: Introductionmentioning

confidence: 99%

“…GlcAT-P glucuronyltransferase activity is also required for proteoglycan and glycoprotein biosynthesis [30], [31]. Another class of proteins modified by GlcAT-P is extracellular matrix (ECM) proteins and some ECM proteins are known to bear the HNK-1 epitope [20]. In Drosophila , production and secretion of several ECM molecules is an essential function of hemocytes [32].…”

Section: Introductionmentioning

confidence: 99%

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The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

2011

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During development, the growth of the animal body is accompanied by a concomitant elongation of the peripheral nerves, which requires the elongation of integrated nerve fibers and the axons projecting therein. Although this process is of fundamental importance to almost all organisms of the animal kingdom, very little is known about the mechanisms regulating this process. Here, we describe the identification and characterization of novel mutant alleles of GlcAT-P, the Drosophila ortholog of the mammalian glucuronyltransferase b3gat1. GlcAT-P mutants reveal shorter larval peripheral nerves and an elongated ventral nerve cord (VNC). We show that GlcAT-P is expressed in a subset of neurons in the central brain hemispheres, in some motoneurons of the ventral nerve cord as well as in central and peripheral nerve glia. We demonstrate that in GlcAT-P mutants the VNC is under tension of shorter peripheral nerves suggesting that the VNC elongates as a consequence of tension imparted by retarded peripheral nerve growth during larval development. We also provide evidence that for growth of peripheral nerve fibers GlcAT-P is critically required in hemocytes; however, glial cells are also important in this process. The glial specific repo gene acts as a modifier of GlcAT-P and loss or reduction of repo function in a GlcAT-P mutant background enhances VNC elongation. We propose a model in which hemocytes are required for aspects of glial cell biology which in turn affects the elongation of peripheral nerves during larval development. Our data also identifies GlcAT-P as a first candidate gene involved in growth of integrated peripheral nerves and therefore establishes Drosophila as an amenable in-vivo model system to study this process at the cellular and molecular level in more detail.

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Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

2011

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“…It has been proposed that these proteoglycans function in regulation of neurite outgrowth and cellular organization within the retina. Molecules bearing GAG epitopes have also been hypothesized to facilitate other functions during ocular development, such as separation of the lens vesicle from the prospective corneal epithelium (Mizuno et al, 1995) and stabilization of the ciliary body and retina (Uusitalo and Kivela, 2001). Interestingly, chondroitin-6-sulfotransferase is expressed strongly in the mouse eye (Uchimura et al, 1998), suggesting that chondroitin-6-sulfate GAGs are important constituents of proteoglycans in the eye in that species.…”

Section: Discussionmentioning

confidence: 99%

Heterogeneity of chondroitin sulfate glycosaminoglycan localization during early development of the striped bass (Morone saxatilis)

et al. 2002

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Recent studies have suggested important functions for proteoglycanassociated chondroitin sulfate glycosaminoglycans (GAGs) during embryonic and larval development in numerous organisms, including the teleost. Little is known, however, about the specific distribution of different chondroitin sulfate GAGs during early development. The present study utilized immunohistochemistry to localize chondroitin sulfate GAG antigens during development of the striped bass (Morone saxatilis). Immunoreagents utilized were monoclonal antibodies (MAbs) TC2, d1C4, and CS-56, which recognize, respectively, native epitopes on glycosaminoglycan chains enriched in chondroitin-4-, chondroitin-6-, and both chondroitin-4-and -6-sulfate. Little or no immunoreactivity was observed in gastrulating embryos at 18 hr postfertilization with any MAb tested. By 24 hr (8 somites), the CS-56 epitope was localized around the notochord. At hatching (48 hr) and early larval (72 hr) stages, d1C4 and CS-56 antigens codistributed in some sites (e.g., the notochord and myosepta), but a striking heterogeneity of chondroitin sulfate GAG localization was observed in other developing tissues, including the eye and specific subsets of basement membrane. At these latter time points, TC2 reacted primarily with the extracellular matrix of the developing heart, particularly the ventricular and conotruncal segments. Heterogeneous patterning of these chondroitin sulfate GAG epitopes suggests dynamic regulation of proteoglycan function during critical morphogenetic events in early development of the striped bass. Anat

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“…Persistent antigenic stimulation or repetitive stimulation/proliferation rounds lead to progressively down-regulation of CD28 expression and accumulation of highly antigen experienced CD8+ CD28 T cells [72, 74]. The decrease of CD28 is associated with the increased expression of CD57 (HNK, Leu-7, L-2) [76, 77], a terminally sulphated carbohydrate-determinant found on various surface glycoproteins, proteoglycans and glycolipids on subsets of natural killer (NK) cells, T cells, and others [72, 78, 79]. …”

Section: Cd28mentioning

confidence: 99%

Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression

et al. 2017

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Despite the advent of many therapeutic agents, such as bortezomib and lenalidomide that have significantly improved the overall survival, multiple myeloma remains an incurable disease. Failure to cure is multifactorial and can be attributed to the underlying genetic heterogeneity of the cancer and to the surrounding micro-environment. Understanding the mutual interaction between myeloma cells and micro-environment may lead to the development of novel treatment strategies able to eradicate this disease. In this review we discuss the principal molecules involved in the micro-environment network in multiple myeloma and the currently available therapies targeting them.

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The HNK-1 Carbohydrate Epitope in the Eye: Basic Science and Functional Implications

Cited by 19 publications

References 173 publications

The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

The Glucuronyltransferase GlcAT-P Is Required for Stretch Growth of Peripheral Nerves in Drosophila

Heterogeneity of chondroitin sulfate glycosaminoglycan localization during early development of the striped bass (Morone saxatilis)

Bone marrow micro-environment is a crucial player for myelomagenesis and disease progression

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