Axonal regeneration from CNS neurons in the cerebellum and brainstem of adult rats: correlation with the patterns of expression and distribution of messenger RNAs for L1, CHL1, c-jun and growth-associated protein-43

Chaisuksunt, Vipavadee; Zhang, Y; Anderson, Patrick N.; Campbell, G.; Vaudano, Elisabetta; Schachner, Melitta; Lieberman, A. R.

doi:10.1016/s0306-4522(00)00254-2

Cited by 94 publications

(81 citation statements)

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“…Similar observations have been made for CHL1 (23). Expression of CHL1 in injured and regenerating central and peripheral neurons is strongly up-regulated (24,25), but its functional role in regeneration remains to be defined. Because specific proteolytic processing of CHL1 may be of functional importance for neuronal survival, neurite outgrowth, and cell migration, we screened for the ability of several members of the family of ADAM metalloproteases to process CHL1 into its naturally occurring fragments.…”

supporting

confidence: 79%

Ectodomain Shedding of the Neural Recognition Molecule CHL1 by the Metalloprotease-disintegrin ADAM8 Promotes Neurite Outgrowth and Suppresses Neuronal Cell Death

Naus

Richter

Wildeboer

et al. 2004

Journal of Biological Chemistry

114

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The neural cell adhesion molecule "close homologue of L1," termed CHL1, has functional importance in the nervous system. CHL1 is expressed as a transmembrane protein of 185 kDa, and ectodomain shedding releases soluble fragments relevant for its physiological function. Here we describe that ADAM8, a member of the family of metalloprotease disintegrins cleaves a CHL1-Fc fusion protein in vitro at two sites corresponding to release of the extracellular domain of CHL1 in fibronectin (FN) domains II (125 kDa) and V (165 kDa), inhibited by batimastat (BB-94). Cleavage of CHL1-Fc in the 125-kDa fragment was not detectable under nonreducing conditions arguing that cleavage resulting in the 165-kDa fragment is more relevant in releasing soluble CHL1 in vivo. In cells transfected with full-length ADAM8, membrane proximal cleavage of CHL1 was similar and not stimulated by phorbol ester 12-O-tetradecanoylphorbol-13-acetate and pervanadate. No cleavage of CHL1 was observed in cells expressing either inactive ADAM8 with a Glu 330 to Gln exchange (EQ-A8), or active ADAM10 and ADAM17. Consequently, processing of CHL1 was hardly detectable in brain extracts of ADAM8-deficient mice but enhanced in a neurodegenerative mouse mutant. CHL1 processed by ADAM8 in supernatants of COS-7 cells and in co-culture with cerebellar granule neurons was very potent in stimulating neurite outgrowth and suppressing neuronal cell death, not observed in cells co-transfected with CHL1/EQ-A8, CHL1/ ADAM10, or CHL1/ADAM17. Taken together, we propose that ADAM8 plays an important role in physiological and pathological cell interactions by a specific release of functional CHL1 from the cell surface.Many membrane-anchored proteins are subjected to proteolytic processing thereby releasing their extracellular domains, a process termed ectodomain shedding (1). This modification causes qualitative and irreversible changes in the function of these molecules. As demonstrated with genetic and biochemical means, enzymes capable of these functions are ADAMs 1 (for "a disintegrin and metalloprotease domain"), proteins that constitute a family of transmembrane glycoproteins with essential physiological roles in fertilization, myogenesis, and neurogenesis (2). These functions are due to distinct protein domains involved in either cell-cell fusion or cell-cell interaction, or to their zinc-coordinating metalloprotease domain. To date, the family of ADAM proteinases comprises more than 30 members in different species (3, 4). Fourteen of the murine ADAMs contain the catalytic consensus sequence HEXXHXXGXXHD in their metalloprotease domains and are therefore predictably proteolytically active (3, 4). The cleavage of myelin basic protein (MBP) by ADAM10/MADM (mammalian disintegrin-metalloprotease) was the first demonstration of proteolysis by ADAMs (5). The TNF-␣ convertase (TACE/ADAM17) was purified on the basis of its ability to cleave TNF-␣ (6, 7) and a number of other peptide and protein substrates in vitro (1,8). TACE is also implicated in the shedding of factors in...

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supporting

confidence: 79%

Ectodomain Shedding of the Neural Recognition Molecule CHL1 by the Metalloprotease-disintegrin ADAM8 Promotes Neurite Outgrowth and Suppresses Neuronal Cell Death

Naus

Richter

Wildeboer

et al. 2004

Journal of Biological Chemistry

114

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“…Similar observations have been made in other CNS neuronal systems (Vaudano et al, 1995;Anderson et al, 1998). Although it is tempting to attribute the observed axonal regeneration to the increase in GAP-43 expression, one should not overlook the fact that these proximal axotomies invariably induce a battery of other RAGs, such as L1 and c-jun (Chaisuksunt et al, 2000), plus many others that may not yet be characterized. The targeted overexpression of GAP-43 with adenoviral vectors, for example, failed to promote the regeneration of Purkinje cell axons into permissive PN transplants (Buffo et al, 1997).…”

Section: Gap-43supporting

confidence: 68%

Promoting axonal regeneration in the central nervous system by enhancing the cell body response to axotomy

Plunet

Kwon

Tetzlaff

2002

J of Neuroscience Research

135

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Neurons projecting into the peripheral nervous system (PNS) regenerate their axons after injury, in contrast to those confined to the central nervous system (CNS). Both neuronal and nonneuronal factors contribute to the lack of CNS regeneration. In this review we concentrate on the differential gene expression response to axotomy in PNS vs. CNS neurons. In general CNS neurons fail to up-regulate or sustain the expression of regenerationassociated proteins (RAGs), including trophic factors and their receptors. The presumed lack of trophic support of axotomized CNS neurons provided the rationale for the exogenous application of trophic factors, either to the lesion site or to the cell bodies. Here, we review our data on the application of trophic factors to rubrospinal and corticospinal neurons. Cell body treatment of axotomized rubrospinal neurons with brain-derived neurotrophic factor (BDNF) reversed atrophy, increased GAP-43 and T␣-1 tubulin mRNA expression, and promoted axonal regeneration into peripheral nerve grafts. Importantly, BDNF cell body treatment was still effective in the chronic setting, i.e., when initiated 1 year after injury, but BDNF had no effect when applied to the chronic spinal cord injury site. The ability to promote regeneration in chronically injured neurons will hopefully contribute to the development of treatment strategies for chronic spinal injuries. © 2002 Wiley-Liss, Inc.It is becoming increasingly evident that several factors are implicated in the failure of central nervous system (CNS) neurons to regenerate their axons after injury. These factors are often conceptualized as being either intrinsic (i.e., related to the native gene expression response of the axotomized CNS neuron) or extrinsic in nature (i.e., related to molecules and/or physical barriers in the CNS environment that inhibit axonal growth). This conceptual differentiation is somewhat an oversimplification, because extrinsic factors such as molecules that influence growth cone motility/guidance may also induce intrinsic factors such as neuronal gene expression. With regard to the extrinsic factors, numerous molecules that are inhibitory to axonal growth have been found in association with CNS myelin and the CNS injury site and have been extensively reviewed elsewhere (Davies et al

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“…L1 is among several growth-associated genes that are upregulated by neurons after nervous system injury (Daniloff, et al, 1986;Chaisuksunt et al, 2000;Kubasak et al, 2005), however its effects are contradictory. Some studies suggest that L1 CAM reiterates its developmental role following injury, as it is upregulated on sprouting and regenerating axons in many models (Daniloff et al, 1986;Martini and Schachner, 1988;Miragall et al, 1989;Styren et al, 1995;Chalmers et al, 1996;Brook et al, 2000;Kubasak et al, 2005;Chen et al, 2007).…”

mentioning

confidence: 99%

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

Runyan

Roy²,

Zhong³

et al. 2007

Neuroscience

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L1 is a cell adhesion molecule associated with axonal outgrowth and fasciculation during spinal cord development and may reiterate its developmental role in adults following injury; L1 is upregulated on certain sprouting and regenerating axons in adults, but it is unclear if L1 expression is necessary for, or contributes to, regrowth of axons. This study asks if L1 is required for small-diameter primary afferents to sprout by conducting unilateral dorsal rhizotomies (6 segments; T10-L2) on both wildtype and L1 mutant mice. First we determined that L1 co-localizes substantially with the peptidergic (calcitonin gene-related peptide; CGRP) but minimally with the nonpeptidergic (isolectin B4; IB4) primary afferents in intact wild-type and L1 mutant mice. However, we encountered a complication using IB4 to identify primary afferents post-rhizotomy; we detected extensive abnormal IB4 expression in the dorsal horn and dorsal columns. Much of this aberrant IB4 labeling is associated with fibrous astrocytes and microglia. Five days after dorsal rhizotomy a large decrease in peptidergic and nonpeptidergic afferents is evident on the deafferented side in both wild-type and L1 mutants. Three months after surgery the peptidergic primary afferents sprouted into the center of the denervated dorsal horn in both wild-type and mutant mice, and quantitative analyses confirmed a sprouting density of similar magnitude in both genotypes. In contrast, we did not detect sprouting in the nonpeptidergic primary afferents in either genotype. These results suggest that the absence of L1 neither diminishes nor enhances sprouting of peptidergic small-diameter primary afferent axons following a dorsal rhizotomy. Keywordscell adhesion molecule; denervated; IB4; CGRP; nociceptors; rhizotomy The cell adhesion molecule L1 (L1 CAM) is an axonal glycoprotein and a member of the immunoglobulin superfamily (Kamiguchi et al., 1997). L1 plays a role in axonal outgrowth, fasciculation, and guidance during spinal cord development (Stallcup et al., 1985;Jessell, 1988;Stoeckli and Landmesser, 1995;Orlino et al., 2000;Tran and Phelps, 2000;Akopians et al., 2003) through homophilic and various heterophilic binding partners such as integrins (αVβ3 and α5β1) and the fibroblast growth factor receptor (Kamiguchi and Lemmon, 1997 Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. Lemmon, 1997;Castellani et al., 2000). NIH Public AccessMutations in X-linked L1 in humans cause major developmental errors and result in a group of symptoms that include corpus callosum hypoplasia, spastic paraplegia and hydrocephalus (Fran...

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Axonal regeneration from CNS neurons in the cerebellum and brainstem of adult rats: correlation with the patterns of expression and distribution of messenger RNAs for L1, CHL1, c-jun and growth-associated protein-43

Cited by 94 publications

References 48 publications

Ectodomain Shedding of the Neural Recognition Molecule CHL1 by the Metalloprotease-disintegrin ADAM8 Promotes Neurite Outgrowth and Suppresses Neuronal Cell Death

Ectodomain Shedding of the Neural Recognition Molecule CHL1 by the Metalloprotease-disintegrin ADAM8 Promotes Neurite Outgrowth and Suppresses Neuronal Cell Death

Promoting axonal regeneration in the central nervous system by enhancing the cell body response to axotomy

L1 cell adhesion molecule is not required for small-diameter primary afferent sprouting after deafferentation

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