Table 1.

Multifunctional HSPGs interactive with dystroglycan.

Protein	Sensory processes affected	Function
Perlecan	Perlecan is cytoprotective and facilitates cell-ECM osmo-mechanosensory instructive cues properties.	The three LamG domains in domain V of perlecan interact with α-DG. Perlecan regulates diverse cellular processes(Whitelock et al. 2008), stabilises tissues, sequesters growth factors/morphogens, regulates tissue development and morphogenesis, cell proliferation/differentiation in chondrogenesis,vasculogenesis, osteogenesis, inflammation, cardiac development, and angiogenesis (Lord et al. 2014; Vincent et al. 2022). Perlecan has mechanosensory, osmoregulatory roles in weight bearing and tensional connective tissues (Zhao et al. 2020; Guilak et al. 2021) and acts as a shear flow biosensor for endothelial cells and osteocytes, regulates SMCs, vascular tone, blood pressure, bone assembly and homeostasis (Thompson et al. 2011; Wang et al. 2014; Wijeratne et al. 2016). Perlecan is a key component of the vascular ECM and maintains endothelial cell barrier function, it inhibits SMC proliferation and maintains vascular homeostasis. Perlecan has roles in the repair of diseased connective tissues (Arikawa-Hirasawa 2022; Hayes et al. 2022; Hayes and Melrose 2023; Zhao et al. 2023). More than 30 HSPG2 mutations lead to Schwartz-Jampel Syndrome (Lin et al. 2021).
Collagen XVIII	Assembly and stabilization of basement membranes	Collagen XVIII stabilises NMJ assembly and function, eye development and maintenance of the BBB basement membranes. Collagen XVIII levels are elevated in cerebrospinal fluid following traumatic brain injury (Chen et al. 2013) and associated with brain lesions(Mueller et al. 2007).
Agrin	Assembly and function of NMJ, regulation of cardiomyocyte function, bioresponsive mechanoreceptor regulated by Hippo cell signaling	Agrin initiates MuSK kinase activity, a receptor tyrosine kinase and a key regulator of NMJ development. Agrin interacts with LRPR, rapsyn and DOK-7 cytoplasmic adaptor protein (Burgess et al. 1999). The NMJ agrin-Lrp4-MuSK cell signaling pathway (Herbst 2020) is disrupted in congenital myasthenia syndromes, Schwartz-Jampel syndrome, Fukuyama-type congenital muscular dystrophy, amyotrophic lateral sclerosis, and sarcopenia. Impaired MuSK signaling causes severe muscle weakness in congenital myasthenic syndromes. DOK7 promotes NMJ regeneration after nerve injury (Kosco et al. 2023), neuronal agrin promotes myoblast proliferation(Gros et al. 2022). Neuronal LRP4 regulates synapse formation and synaptic plasticity (Karakatsani et al. 2017). Mechanosensitive Yap/Taz effectors of Hippo cell signaling regulate cardiomyocyte replication/regeneration through Agrin.
α, β, γ Neurexin	Pre/Post Synaptic organization and function	Neurexins have cell adhesive functional interactions with several hundred synaptic proteins providing diversity and specificity in synaptic activity (Dai et al. 2022; Traunmüller et al. 2023). Stabilization of neural pre-and post synaptic terminal interconnections promote neurotransduction efficiency and synaptic plasticity in neural networks (Kim et al. 2022). Neurexin multi-protein complexes regulate pre-synaptic voltage gated Ca channels and functional neuronal receptors (Noborn and Sterky 2023) in health and disease (Cuttler et al. 2021).
Eyes Shut (Eys)	Photoreceptor stabilization and function	Eyes shut interacts with matriglycan O-mannosyl glycans on α-DG to stabilise the photoreceptor ribbon synapse in phototransductive interactions with retinal bipolar neurons (Husain et al. 2006; Liu et al. 2020), maintain photoreceptor morphology and visual acuity. Mutations in Eys result in vision impairment in retinitis pigmentosa (Suvannaboon et al. 2022).
Pikachurin	Photoreceptor stabilization and function	Pikachurin stabilises the photoreceptor axoneme cilium and ribbon synapse (Sugita et al. 2015; Furukawa et al. 2020), interacts with orphan receptor GPR179 (Orlandi et al. 2012; Orlandi et al. 2018) and α-DG in phototransduction (Furukawa et al. 2020) involving bipolar neurons of the retinal neural network essential in vision (Sato et al. 2008; Omori et al. 2012; Orlandi et al. 2018; Furukawa et al. 2020). LamG-domains interact with α-DG.