What is it about?

The NG2/CSPG4 gene encodes a transmembrane proteoglycan (PG) representing the largest and most structurally complex cell surface-associated molecule of the human proteome. The NG2/CSPG4 transcript shows remarkable evolutionary conservation and, due to the extensive intracellular processing of the translated protein, it generates an array of glycoforms with the potential to execute a wide spectrum of variant-specific molecular interactions. These molecular events are articulated throughout the coaxing of more than 40 ligand molecules and are concurrently operated by the ectodomain and the cytoplasmic tail, whose phosphorylation is tightly controlled by cross-talking signaling pathways. Owing to the multitude of molecular interplays that the PG engages, NG2/CSPG4 stand out for its unique capability to influence virtually all cellular phenomena, spanning from those critically involved in the early phases of embryonic development to those purporting pathological conditions. We discuss here the progresses made in advancing our understanding about the structural-functional bases for the unparalleled ability of NG2/CSPG4 to widely impact on cell behaviour and how its multivalency may be exploited to interfere with disease progression.

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Why is it important?

The review article discusses aspects of the multifunctionality of NG2/CSPG4 which have not been dwelled upon in earlier essays. In particular it highlights how the different domains of the macromolecule may engagé different types of molecular interactions with a myriad of ligands, and how these interactions how crucial for cellular functions.


NG2/CSPG4 is a multivalent cell surface component controlling numerous cellular phenomena. As such it has a strong value as a prognostic and therapeutic oncogenic factor, but it also plays important roles in other in other pathological conditions, such e.g. neuorlogical diseases. A better understanding of the modes through which it may operate opens therefore up new opportunities to better grasp the dynamics of cellular events and its exploitation in clinical contexts.

Roberto PERRIS
Universita degli Studi di Parma

Read the Original

This page is a summary of: Structural deciphering of the NG2/CSPG4 proteoglycan multifunctionality, The FASEB Journal, December 2018, Federation of American Societies For Experimental Biology (FASEB), DOI: 10.1096/fj.201801670r.
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