Metalloproteinase-mediated release of the ectodomain of L1 adhesion molecule

Beer, Sandra; Oleszewski, Matthias; Gutwein, Paul; Geiger, Claudia; Altevogt, Peter

doi:10.1242/jcs.112.16.2667

Cited by 73 publications

(1 citation statement)

References 61 publications

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“…To test the contribution of L1 to OB-OEC PM-stimulated CST outgrowth, we used a monoclonal L1 functionblocking antibody (clone 324), previously demonstrated to inhibit fibroblast matrix remodeling (Di Sciullo et al, 1998) and inhibit migration of B16F10 melanoma cells (Beer et al, 1999). OB-OEC or control CHO-R2 PM was preincubated with either control IgG antibodies, or anti-L1 antibodies, before CST neurons were plated to assay outgrowth.…”

Section: L1 In Oec Pm Contributes To the Cst Axon Elongation Activity...mentioning

confidence: 99%

Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM‐dependent mechanism

Witheford

Westendorf

Roskams

2013

Glia

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Olfactory ensheathing cells (OECs) support the ability of the olfactory neuraxis to continually retarget within the mature central nervous system. This has led many groups to transplant OECS into the lesioned rodent spinal cord (SCd) in vivo, with variable degrees of anatomical, physiological, and behavioral success. Some of the most conflicting results in OEC transplantation have come from the corticospinal tract (CST) which has shown a relatively poor regeneration response. Although spinal neurite sprouting occurs in response to OECs in vivo and in vitro, we do not know if OECs possess the molecular machinery to stimulate outgrowth of functionally important motor tracts like the CST. Here, we assay cultured postnatal day 8 mouse CST neurons expressing yellow fluorescent protein (YFP) for their ability to extend axons and dendrites in response to different glia, and show that CST axons elongate in response to proteins in OEC plasma membrane (PM). In contrast, CST dendritic branching preferentially occurs in response to factors secreted by both OECs and astrocytes. We identify the L1-neural cell adhesion molecule (L1-NCAM) as a major component of OEC-induced corticospinal axon elongation, and have determined that OEC PM factors (including L1), can stimulate CST outgrowth even when inhibition is induced by myelin associated glycoprotein. Together, these results suggest that in the right context, OEC-derived PM factors could enhance CST axonal regeneration, and potentially contribute to approaches to ameliorate recovery from SCd injury.

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Section: L1 In Oec Pm Contributes To the Cst Axon Elongation Activity...mentioning

confidence: 99%

Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM‐dependent mechanism

Witheford

Westendorf

Roskams

2013

Glia

View full text Add to dashboard Cite

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Molecular and Cellular Mechanisms of Ectodomain Shedding

Hayashida

Bartlett

Chen

et al. 2010

The Anatomical Record

152

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The extracellular domain of several membrane-anchored proteins is released from the cell surface as soluble proteins through a regulated proteolytic mechanism called ectodomain shedding. Cells use ectodomain shedding to actively regulate the expression and function of surface molecules, and modulate a wide variety of cellular and physiological processes. Ectodomain shedding rapidly converts membrane-associated proteins into soluble effectors and, at the same time, rapidly reduces the level of cell surface expression. For some proteins, ectodomain shedding is also a prerequisite for intramembrane proteolysis, which liberates the cytoplasmic domain of the affected molecule and associated signaling factors to regulate transcription. Ectodomain shedding is a process that is highly regulated by specific agonists, antagonists, and intracellular signaling pathways. Moreover, only about 2% of cell surface proteins are released from the surface by ectodomain shedding, indicating that cells selectively shed their protein ectodomains. This review will describe the molecular and cellular mechanisms of ectodomain shedding, and discuss its major functions in lung development and disease.

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(Make) Stick and cut loose—Disintegrin metalloproteases in development and disease

et al. 2006

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"A disintegrin and metalloprotease" (ADAM) proteases form a still growing family of about 40 type 1 transmembrane proteins. They are defined by a common modular ectodomain architecture that combines cell deadhesion/adhesion and fusion motifs (disintegrin and cysteine-rich domains), with a Zn-protease domain capped by a large prodomain. Their ectodomain thus strikingly resembles snake venom disintegrin proteases, which by combined integrin blocking and extracellular proteolysis, can cause extensive tissue damage after snake bites. A surprisingly large proportion (13 ADAMs) is exclusively expressed in the male gonads, and only a minority can be found throughout all tissues. As predicted by their amino acid sequence, a major proportion of this family has not maintained a functional protease domain, most probably rendering them into pure adhesion and/or fusion proteins. For most ADAMs, the respective key function has remained elusive. Despite their overall conserved ectodomain structure, ADAMs appear to be subdivided into those with a predominant role in direct adhesion (e.g., ADAMs 1, 2, and 3) and those mainly acting as proteases (e.g., ADAMs 10 and 17). Only for a few of them are functions of more than one domain documented (e.g., ADAM9 in cell fusion and proteolysis). Several ADAMs exist in both membrane-resident and secreted isoforms; the functional significance of this dichotomy is in most cases still unclear. Knockout phenotypes have been informative only in a few cases (ADAMs 1, 2, 10, 12, 15, 17, and 19) and are mainly related to their protease function. A common denominator of ADAM-mediated proteolysis is the ectodomain shedding of a broad spectrum of substrates, including paracrine growth factors like epidermal growth factor receptor (EGFR) ligands, cell adhesion molecules like CD44 or cadherins, and the initiation of regulated intramembrane proteolysis (RIP), whereby the transmembrane fragment of the respective substrate is further cleaved by an intramembrane cleaving protease to release an intracellular domain acting as a nuclear transcription regulator. Most ADAMs feature a significant overlap of substrate specificities, explaining why an inactivation of individual ADAMs only rarely causes major phenotypes.

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Metalloproteinase-mediated release of the ectodomain of L1 adhesion molecule

Cited by 73 publications

References 61 publications

Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM‐dependent mechanism

Olfactory ensheathing cells promote corticospinal axonal outgrowth by a L1 CAM‐dependent mechanism

Molecular and Cellular Mechanisms of Ectodomain Shedding

(Make) Stick and cut loose—Disintegrin metalloproteases in development and disease

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