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dc.contributor.authorFarach-Carson, Mary C.
Warren, Curtis R.
Harrington, Daniel A.
Carson, Daniel D.
dc.date.accessioned 2016-02-02T19:17:43Z
dc.date.available 2016-02-02T19:17:43Z
dc.date.issued 2014
dc.identifier.citation Farach-Carson, Mary C., Warren, Curtis R., Harrington, Daniel A., et al.. "Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders." Matrix Biology, 34, (2014) Elsevier: 64-79. http://dx.doi.org/10.1016/j.matbio.2013.08.004.
dc.identifier.urihttps://hdl.handle.net/1911/88298
dc.description.abstract The extracellular matrix proteoglycan (ECM) perlecan, also known as heparan sulfate proteoglycan 2 or HSPG2, is one of the largest (>ᅠ200ᅠnm) and oldest (>ᅠ550ᅠMᅠyears) extracellular matrix molecules. In vertebrates, perlecan's five-domain structure contains numerous independently folding modules with sequence similarities to other ECM proteins, all connected like cars into one long, diverse complex train following a unique N-terminal domain I decorated with three long glycosaminoglycan chains, and an additional glycosaminoglycan attachment site in the C-terminal domain V. In lower invertebrates, perlecan is not typically a proteoglycan, possessing the majority of the core protein modules, but lacking domain I where the attachment sites for glycosaminoglycan chains are located. This suggests that uniting the heparan sulfate binding growth factor functions of domain I and the core protein functions of the rest of the molecule in domains IIヨV occurred later in evolution for a new functional purpose. In this review, we surveyed several decades of pertinent literature to ask a fundamental question: Why did nature design this protein uniquely as an extraordinarily long multifunctional proteoglycan with a single promoter regulating expression, rather than separating these functions into individual proteins that could be independently regulated? We arrived at the conclusion that the concentration of perlecan at functional borders separating tissues and tissue layers is an ancient key function of the core protein. The addition of the heparan sulfate chains in domain I likely occurred as an additional means of binding the core protein to other ECM proteins in territorial matrices and basement membranes, and as a means to reserve growth factors in an on-site depot to assist with rapid repair of those borders when compromised, such as would occur during wounding. We propose a function for perlecan that extends its role from that of an extracellular scaffold, as we previously suggested, to that of a critical agent for establishing and patrolling tissue borders in complex tissues in metazoans. We also propose that understanding these unique functions of the individual portions of the perlecan molecule can provide new insights and tools for engineering of complex multi-layered tissues including providing the necessary cues for establishing neotissue borders.
dc.language.iso eng
dc.publisher Elsevier
dc.rights Open access under CC BY-NC-ND license.
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/
dc.title Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders
dc.type Journal article
dc.contributor.funder National Institutes of Health, National Cancer Institute
dc.contributor.funder National Institutes of Health, National Institute of Dental and Craniofacial Research
dc.citation.journalTitle Matrix Biology
dc.subject.keywordPerlecan
HSPG2
Basement membrane
Basal lamina
Heparan sulfate
Proteoglycan
tissue structure
tissue borders
dc.citation.volumeNumber 34
dc.type.dcmi Text
dc.identifier.doihttp://dx.doi.org/10.1016/j.matbio.2013.08.004
dc.identifier.pmcid PMC3938997
dc.identifier.pmid 24001398
dc.identifier.grantID PO1 CA98912 (National Institutes of Health, National Cancer Institute)
dc.identifier.grantID DE022969 (National Institutes of Health, National Institute of Dental and Craniofacial Research)
dc.type.publication publisher version
dc.citation.firstpage 64
dc.citation.lastpage 79


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