Table I.
The biodiverse structural forms and functions of KS proteoglycans
| Protein | Distribution | Functions | Reference |
|---|---|---|---|
| KS–proteoglycans of tensional and weight-bearing connective tissues | |||
| Aggrecan lectican KS/CSPG | Large ECM PG of cartilage, CNS, tendon, IVD | Tissue hydration, weight bearing. Inhibits neurite outgrowth, repulsive cue on axonal guidance | Fryer et al. (1992), Kiani et al. (2002) |
| Fibromodulin | Widespread ECM distribution in cornea, cartilage, tendon, IVD, meniscus | Regulate collagen fibrillogenesis and inflammatory cytokines/growth factors, cell proliferation and cell signaling. Lumican is a tumor marker | Chen and Birk (2013), Merline et al. (2009), Schaefer and Iozzo (2008) |
| Keratocan | Blochberger et al. (1992), Corpuz et al. (1996), Oldberg et al. (1989), Sommarin et al. (1998) | ||
| Lumican | |||
| Osteoadherin (osteomodulin) | Cartilage/bone growth plate interface | Cell binding bone KSPG, may regulate mineralization | Sommarin et al. (1998) |
| Mimecan (osteoglycin) | Broad distribution in connective tissues | Corneal mimecan is sulfated but not sulfated in other tissues. Has roles in bone induction | Corpuz et al. (2000), Funderburgh et al. (1997) |
| CD44 | Epidermal/CNS KS-CD44 isoform | Ubiquitous HA receptor occurring as alternatively spliced forms substituted with KS, CS or HS | Takahashi et al. (1996) |
| Bone sialoprotein-II (BSP-II) | 80 kDa core protein, substituted with sialic acid and N- and O-linked KS chains | BSP-II, KSPG in compact rabbit bone, BSP-II from other species does not contain KS. Related KSPG identified in rat calvaria BSP-II in medullary bone in laying birds is a KSPG | Ganss et al. (1999), Hadley et al. (2016), Kinne and Fisher (1987), Masubuchi et al. (1975), Nakamura et al. (2001) |
| KS–proteoglycans of mucinous tissues | |||
| MUC1 | epithelial distribution | transmembrane epithelial KSPG, heavily O-glycosylated, sialylated forms 200–500 nm layer on cell surface | Aplin et al. (1998), Brayman et al. (2004) |
| Endometrial ECM | |||
| Mucous KSPG | 220 kDa 5D4+ve KSPG | KSPG of cervical mucous secretions | Fischer et al. (2001) |
| Podocalyxcin | 240 kDa 3–10 G +ve | Mucin-like, sialomucin cell surface KS–PG related to CD34. Anti-adhesive. Widespread epithelial distribution | Nielsen and McNagny (2009), Vitureira et al. (2010) |
| Zona pellucida protein-3 (PZP-3) | zona pellucida | An N-linked polylactosamine sulfated KS protein with oocyte–sperm receptor interactive activity | Nakano et al. (1996), Noguchi and Nakano (1992) |
| Oocyte membrane glycoprotein | |||
| Keratinocyte perlecan | Epidermis | Hybrid KS-HS-CS basement membrane proteoglycan with roles in ECM stabilization and growth factor binding | Knox et al. (2005) |
| Embryoglycan | Cell surface PG of Pluripotent and early embryonic stem cells | Highly branched polylactosamine non-sulfated KS chains contain 3-G10, EMCA-2, 3, TRA-1-60 and TRA-1-81, GCTM-2, SSEA carbohydrate motifs | Dvorak et al. (1998), Muramatsu (2017), Ozawa et al. (1985a) |
| KS–proteoglycans of the PNS/CNS | |||
| Abakan | Astrocyte KSPG, co-distributed with glial fibrillary acidic protein | Provides repulsive axonal guidance cues which regulate neuritogenesis in CNS development | Geisert and Bidanset (1993) |
| Claustrin/MAP1B | Claustrin, ECM PG synthesized by CNS astrocytes. MAP1B is a microtubule associated protein | Claustrin, anti-adhesive neural proteoglycan inhibits neurite outgrowth, N-terminal truncated MAP-1B, a 225 kDa microtubule and dendritic PG of neurons and glial cells | Burg and Cole (1994), Edelmann et al. (1996) |
| Synapse vesicle protein 2 (SV2) | 12 span membrane KSPG, 100/250 kDa forms and 3 isoforms SV2A, B, C | Storage/neurotransmitter transport in synaptic vesicles/neuroendocrine cells. KS of SV2 interactive component of a smart gel delivery system | Bajjalieh et al. (1993), Feany et al. (1992), Scranton et al. (1993) |
| PG1000 | KS/CS proteoglycan Electric organ ECM | Forms 2–6 monomer complexes concentrated in the reticular laminae of electric organ basement membranes surrounding nerve fibers/terminals | Carlson et al. (1996), Iwata and Carlson (1991) |
| Phosphacan, RPTP-β/PTPζ, (DSD-1 in mice) | PNS, CNS KSPG also has CS and HNK-1 substitution. Phosphacan is the ecto-domain of PTPζ | PTPζ is a type I transmembrane glycoprotein, carbonic anhydrase motif interacts with pleiotrophin and midkine to promote neurite outgrowth activity | Faissner et al. (2006), Garwood et al. (1999), Morise et al. (2014) |
| Miscellaneous KS-substituted proteins | |||
| Transferrin, thyroglobulin | Associated with papillary thyroid carcinoma | KS epitope is capped with α2-3 N-acetylneuraminic acid | Magro et al. (2003) |
| Cytokeratin | epidermal protein | Human keratinocytes contain keratin filaments containing KS chains | Schafer and Sorrell (1993) |
| Prostaglandin-D synthase | 28 kDa KS-glycoprotein produced by bovine corneal keratocytes | Corneal retinoid transporter, also found in seminal plasma, rat brain and spinal cord, rat cochlea, human prostate, human and rat epididymis and testes | Berryhill et al. (2001) |
| Mammallin | Avian KS proteoglycan | Role in egg shell production, binds Ca2+ and maintains a Calcium reserve. Mammallin awaits full characterization. The KS content of egg shells correlates directly with their strength | Du et al. (2015), Ha et al. (2007) |
CNS, central nervous system; SV2, synaptic vesicle protein 2; RPTPβ, receptor protein tyrosine phosphatase β; PTP ζ, protein tyrosine phosphatase ζ.