Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders

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dc.citation.firstpage64en_US
dc.citation.journalTitleMatrix Biologyen_US
dc.citation.lastpage79en_US
dc.citation.volumeNumber34en_US
dc.contributor.authorFarach-Carson, Mary C.en_US
dc.contributor.authorWarren, Curtis R.en_US
dc.contributor.authorHarrington, Daniel Antonen_US
dc.contributor.authorCarson, Daniel D.en_US
dc.date.accessioned2016-02-02T19:17:43Zen_US
dc.date.available2016-02-02T19:17:43Zen_US
dc.date.issued2014en_US
dc.description.abstractThe 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.en_US
dc.identifier.citationFarach-Carson, Mary C., Warren, Curtis R., Harrington, Daniel Anton, et al.. "Border patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue borders." <i>Matrix Biology,</i> 34, (2014) Elsevier: 64-79. http://dx.doi.org/10.1016/j.matbio.2013.08.004.en_US
dc.identifier.doihttp://dx.doi.org/10.1016/j.matbio.2013.08.004en_US
dc.identifier.urihttps://hdl.handle.net/1911/88298en_US
dc.language.isoengen_US
dc.publisherElsevieren_US
dc.rightsOpen access under CC BY-NC-ND license.en_US
dc.rights.urihttp://creativecommons.org/licenses/by-nc-nd/4.0/en_US
dc.subject.keywordPerlecanen_US
dc.subject.keywordHSPG2en_US
dc.subject.keywordBasement membraneen_US
dc.subject.keywordBasal laminaen_US
dc.subject.keywordHeparan sulfateen_US
dc.subject.keywordProteoglycanen_US
dc.subject.keywordtissue structureen_US
dc.subject.keywordtissue bordersen_US
dc.titleBorder patrol: Insights into the unique role of perlecan/heparan sulfate proteoglycan 2 at cell and tissue bordersen_US
dc.typeJournal articleen_US
dc.type.dcmiTexten_US
dc.type.publicationpublisher versionen_US
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