Galactosyl transferase-dependence of neurite outgrowth on substratum-bound laminin

Development ◽  
1990 ◽  
Vol 110 (4) ◽  
pp. 1101-1114 ◽  
Author(s):  
W.A. Thomas ◽  
A.W. Schaefer ◽  
R.M. Treadway
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Neurite Outgrowth ◽  
Dorsal Root ◽  
Axonal Guidance ◽  
Neurite Elongation ◽  
Galactosyl Transferase ◽  
Cellular Events ◽  
Nerve Growth Cone

The cell surface enzyme beta 1–4 galactosyl transferase (galtase) has been implicated in a number of cellular events involving adhesion and recognition, among them migration of neural crest and mesenchymal cells as well as initiation and elongation of neurites from PC12 cells. Results presented here demonstrate that reagents that specifically alter galtase activity modulate the rate of neurite outgrowth from chick dorsal root ganglia on substrata coated with the large extracellular matrix glycoprotein, laminin (LN), a known substrate for galtase activity. Not all neurites responded equally to reagent addition, and in every experiment a subset of neurites was ostensibly unaffected by reagent, even at the highest concentration tested. Those neurites that were affected demonstrated an ability to adapt to the continued presence of reagent and resume normal elongation. These results support the hypothesis that cell surface galtase activity plays an important role in mediating neurite elongation and suggest further that differential expression of galtase at the nerve growth cone might contribute to axonal guidance through glycoconjugate-rich environments in vivo.

scholarly journals Embryonic neural retinal cell response to extracellular matrix proteins: developmental changes and effects of the cell substratum attachment antibody (CSAT).

1987 ◽  
Vol 104 (3) ◽  
pp. 623-634 ◽  
Author(s):  
D E Hall ◽  
K M Neugebauer ◽  
L F Reichardt
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Neurite Outgrowth ◽  
Cellular Response ◽  
Cell Attachment ◽  
Collagen Iv ◽  
Substrate Preference ◽  
Retinal Cell ◽  
Retinal Cells ◽  
Cell Surface Glycoprotein

Cell attachment and neurite outgrowth by embryonic neural retinal cells were measured in separate quantitative assays to define differences in substrate preference and to demonstrate developmentally regulated changes in cellular response to different extracellular matrix glycoproteins. Cells attached to laminin, fibronectin, and collagen IV in a concentration-dependent fashion, though fibronectin was less effective for attachment than the other two substrates. Neurite outgrowth was much more extensive on laminin than on fibronectin or collagen IV. These results suggest that different substrates have distinct effects on neuronal differentiation. Neural retinal cell attachment and neurite outgrowth were inhibited on all three substrates by two antibodies, cell substratum attachment antibody (CSAT) and JG22, which recognize a cell surface glycoprotein complex required for cell interactions with several extracellular matrix constituents. In addition, retinal cells grew neurites on substrates coated with the CSAT antibodies. These results suggest that cell surface molecules recognized by this antibody are directly involved in cell attachment and neurite extension. Neural retinal cells from embryos of different ages varied in their capacity to interact with extracellular matrix substrates. Cells of all ages, embryonic day 6 (E6) to E12, attached to collagen IV and CSAT antibody substrates. In contrast, cell attachment to laminin and fibronectin diminished with increasing embryonic age. Age-dependent differences were found in the profile of proteins precipitated by the CSAT antibody, raising the possibility that modifications of these proteins are responsible for the dramatic changes in substrate preference of retinal cells between E6 and E12.

scholarly journals Thrombospondin-4, an extracellular matrix protein expressed in the developing and adult nervous system promotes neurite outgrowth.

1995 ◽  
Vol 131 (4) ◽  
pp. 1083-1094 ◽  
Author(s):  
S Arber ◽  
P Caroni
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Nervous System ◽  
Neuromuscular Junction ◽  
Neurite Outgrowth ◽  
Adult Skeletal Muscle ◽  
Wide Range ◽  
Thrombospondin 4

Extracellular matrix (ECM) molecules are involved in multiple aspects of cell-to-cell signaling during development and in the adult. In nervous system development, specific recognition processes, e.g., during axonal pathfinding and synaptogenesis involve modulation and signaling by ECM components. Much less is known about their presence and possible roles in the adult nervous system. We now report that thrombospondin-4 (TSP-4), a recently discovered member of the TSP gene family is expressed by neurons, promotes neurite outgrowth, and accumulates at the neuromuscular junction and at certain synapse-rich structures in the adult. To search for muscle genes that may be involved in neuromuscular signaling, we isolated cDNAs induced in adult skeletal muscle by denervation. One of these cDNAs coded for the rat homologue of TSP-4. In skeletal muscle, it was expressed by muscle interstitial cells. The transcript was further detected in heart and in the developing and adult nervous system, where it was expressed by a wide range of neurons. An antiserum to the unique carboxyl-terminal end of the protein allowed to specifically detect TSP-4 in transfected cells in vitro and on cryostat sections in situ. TSP-4 associated with ECM structures in vitro and in vivo. In the adult, it accumulated at the neuromuscular junction and at synapse-rich structures in the cerebellum and retina. To analyze possible activities of TSP-4 towards neurons, we carried out coculture experiments with stably transfected COS cells and motor, sensory, or retina neurons. These experiments revealed that TSP-4 was a preferred substrate for these neurons, and promoted neurite outgrowth. The results establish TSP-4 as a neuronal ECM protein associated with certain synapse-rich structures in the adult. Its activity towards embryonic neurons in vitro and its distribution in vivo suggest that it may be involved in local signaling in the developing and adult nervous system.

scholarly journals Recombinant fish neurotrophin-6 is a heparin-binding glycoprotein: implications for a role in axonal guidance

1997 ◽  
Vol 324 (2) ◽  
pp. 461-466 ◽  
Author(s):  
Xiaoling LI ◽  
Juliane FRANZ ◽  
Friedrich LOTTSPEICH ◽  
Rudolf GÖTZ
Keyword(s):  
Neurite Outgrowth ◽  
Recombinant Baculovirus ◽  
Collagen Gel ◽  
Axonal Guidance ◽  
Heparin Binding ◽  
Protease Cleavage ◽  
Binding Glycoprotein ◽  
Collagen Gel Matrix

Neurotrophin-6 (NT-6) was identified in the teleost fish Xiphophorus as a new member of the neurotrophin gene family. NT-6 binds specifically the glycosaminoglycan heparin. In this study NT-6 was expressed in a stably transfected mammalian cell line, and in insect cells via a recombinant baculovirus. It was purified to homogeneity and characterized by MS and N-terminal sequencing. NT-6 from both expression systems was proteolytically processed at one of two protease cleavage motifs and was found to be glycosylated. It supported the survival of embryonic chick sensory neurons; half-maximal survival was observed at 100 ng/ml. Furthermore, NT-6 elicited neurite outgrowth in explanted embryonic dorsal root ganglia. Addition of heparin into the medium did not potentiate the activity of NT-6 in survival assays. However, when a sensory ganglion explant was cultured in a collagen gel matrix assay adjacent to a heparin bead coated with NT-6, neurite outgrowth directed towards the bead was observed. This indicated that NT-6 was slowly released from the heparin bead generating a concentration gradient of NT-6 instrumental for axonal guidance in vitro. Thus the interaction of NT-6 with heparin might not be required for the activation of the cellular receptor for NT-6 on responsive cells but rather may serve to control, in vivo, the distribution of NT-6.

scholarly journals Ganglioside glycosyltransferases and newly synthesized gangliosides are excluded from detergent-insoluble complexes of Golgi membranes

2004 ◽  
Vol 377 (3) ◽  
pp. 561-568 ◽  
Author(s):  
Pilar M. CRESPO ◽  
Adolfo R. ZURITA ◽  
Claudio G. GIRAUDO ◽  
Hugo J. F. MACCIONI ◽  
Jose L. DANIOTTI
Keyword(s):  
Plasma Membrane ◽  
Cell Surface ◽  
Secretory Pathway ◽  
Chinese Hamster ◽  
Galactosyl Transferase ◽  
Golgi Membranes ◽  
Cell Clones ◽  
Triton X ◽  
Ganglioside Species

GEM (glycosphingolipid-enriched microdomains) are specialized detergent-resistant domains of the plasma membrane in which some gangliosides concentrate. Although genesis of GEM is considered to occur in the Golgi complex, where the synthesis of gangliosides also occurs, the issue concerning the incorporation of ganglioside species into GEM is still poorly understood. In this work, using Chinese hamster ovary K1 cell clones with different glycolipid compositions, we compared the behaviour with cold Triton X-100 solubilization of plasma membrane ganglioside species with the same species newly synthesized in Golgi membranes. We also investigated whether three ganglioside glycosyltransferases (a sialyl-, a N-acetylgalactosaminyl- and a galactosyl-transferase) are included or excluded from GEM in Golgi membranes. Our data show that an important fraction of plasma membrane GM3, and most GD3 and GT3, reside in GEM. Immunocytochemical examination of GD3-expressing cells showed GD3 to be distributed as cold-detergent-resistant patches in the plasma membrane. These patches did not co-localize with a glycosylphosphatidylinositol-anchored protein used as GEM marker, indicating a heterogeneous composition of plasma membrane GEM. In Golgi membranes we were unable to find evidence for GEM localization of either ganglioside glycosyltransferases or newly synthesized gangliosides. Since the same ganglioside species appear in plasma membrane GEM, it was concluded that in vivo nascent GD3, GT3 and GM3 segregate from their synthesizing transferases and then enter GEM. This latter event could have taken place shortly after synthesis in the Golgi cisternae, along the secretory pathway and/or at the cell surface.

Interactions of VEGF isoforms with VEGFR-1, VEGFR-2, and neuropilin in vivo: a computational model of human skeletal muscle

2007 ◽  
Vol 292 (1) ◽  
pp. H459-H474 ◽  
Author(s):  
Feilim Mac Gabhann ◽  
Aleksander S. Popel
Keyword(s):  
Skeletal Muscle ◽  
Extracellular Matrix ◽  
Cell Surface ◽  
Computational Model ◽  
Receptor Activation ◽  
Cell Surface Receptors ◽  
Vastus Lateralis Muscle ◽  
Surface Receptors ◽  
Vegf Isoforms

The vascular endothelial growth factor (VEGF) family of cytokines is involved in the maintenance of existing adult blood vessels as well as in angiogenesis, the sprouting of new vessels. To study the proangiogenic activation of VEGF receptors (VEGFRs) by VEGF family members in skeletal muscle, we develop a computational model of VEGF isoforms (VEGF121, VEGF165), their cell surface receptors, and the extracellular matrix in in vivo tissue. We build upon our validated model of the biochemical interactions between VEGF isoforms and receptor tyrosine kinases (VEGFR-1 and VEGFR-2) and nonsignaling neuropilin-1 coreceptors in vitro. The model is general and could be applied to any tissue; here we apply the model to simulate the transport of VEGF isoforms in human vastus lateralis muscle, which is extensively studied in physiological experiments. The simulations predict the distribution of VEGF isoforms in resting (nonexercising) muscle and the activation of VEGFR signaling. Little of the VEGF protein in muscle is present as free, unbound extracellular cytokine; the majority is bound to the cell surface receptors or to the extracellular matrix. However, interstitial sequestration of VEGF165 does not affect steady-state receptor binding. In the absence of neuropilin, VEGF121 and VEGF165 behave similarly, but neuropilin enhances the binding of VEGF165 to VEGFR-2. This model is the first to study VEGF tissue distribution and receptor activation in human muscle, and it provides a platform for the design and evaluation of therapeutic approaches.

scholarly journals PDZD8 mediated lipid transfer at ER-LE/lys contacts is required for LE/lys positioning and neurite outgrowth

2021 ◽  
pp. jcs.255026
Author(s):  
Yuan Gao ◽  
Juan Xiong ◽  
Qing-Zhu Chu ◽  
Wei-Ke Ji
Keyword(s):  
Neurite Outgrowth ◽  
Neurological Diseases ◽  
Lipid Binding ◽  
Lipid Transfer ◽  
Cellular Functions ◽  
Interacting Protein ◽  
Membrane Contact Sites ◽  
Cellular Events

Membrane contact sites (MCSs) between endoplasmic reticulum (ER) and late endosomes/lysosomes (LE/lys) are emerging as critical hubs for diverse cellular events, and changes in their extents are linked to severe neurological diseases. While recent studies show that synaptotagmin-like mitochondrial-lipid-binding (SMP) domain-containing protein PDZD8 may mediate the ER-LE/lys MCSs, the cellular functions of PDZD8 remain largely elusive. Here we attempt to investigate lipid transfer activities of PDZD8 and the extent to which its cellular functions depend on its lipid transfer activities. In accordance with recent studies, we demonstrate that PDZD8 is a Protrudin-interacting protein and PDZD8 acts as a tether at ER-LE/lys MCSs. Further, we discover that the SMP domain of PDZD8 binds glycerophospholipids and ceramides both in vivo and in vitro, and the SMP domain can transport lipids between membranes in vitro. Functionally, PDZD8 is required for LE/lys positioning and neurite outgrowth, which is dependent on the lipid transfer activity of the SMP domain.

scholarly journals The Ret receptor regulates sensory neuron dendrite growth and integrin mediated adhesion

eLife ◽  
2015 ◽  
Vol 4 ◽  
Author(s):  
Peter Soba ◽  
Chun Han ◽  
Yi Zheng ◽  
Daniel Perea ◽  
Irene Miguel-Aliaga ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Axon Guidance ◽  
Essential Role ◽  
Receptive Fields ◽  
Dendrite Development ◽  
Neuron Dendrite ◽  
Important Regulator ◽  
Class Iv

Neurons develop highly stereotyped receptive fields by coordinated growth of their dendrites. Although cell surface cues play a major role in this process, few dendrite specific signals have been identified to date. We conducted an in vivo RNAi screen in Drosophila class IV dendritic arborization (C4da) neurons and identified the conserved Ret receptor, known to play a role in axon guidance, as an important regulator of dendrite development. The loss of Ret results in severe dendrite defects due to loss of extracellular matrix adhesion, thus impairing growth within a 2D plane. We provide evidence that Ret interacts with integrins to regulate dendrite adhesion via rac1. In addition, Ret is required for dendrite stability and normal F-actin distribution suggesting it has an essential role in dendrite maintenance. We propose novel functions for Ret as a regulator in dendrite patterning and adhesion distinct from its role in axon guidance.

scholarly journals cGMP-mediated signaling via cGKIα is required for the guidance and connectivity of sensory axons

2002 ◽  
Vol 159 (3) ◽  
pp. 489-498 ◽  
Author(s):  
Hannes Schmidt ◽  
Matthias Werner ◽  
Paul A. Heppenstall ◽  
Mechthild Henning ◽  
Margret I. Moré ◽  
...  
Keyword(s):  
Spinal Cord ◽  
Dorsal Root ◽  
In Vitro Studies ◽  
Axonal Guidance ◽  
Dorsal Funiculus ◽  
Spinal Cord Neurons ◽  
Sensory Axons ◽  
Deficient Mice

Previous in vitro studies using cGMP or cAMP revealed a cross-talk between signaling mechanisms activated by axonal guidance receptors. However, the molecular elements modulated by cyclic nucleotides in growth cones are not well understood. cGMP is a second messenger with several distinct targets including cGMP-dependent protein kinase I (cGKI). Our studies indicated that the α isoform of cGKI is predominantly expressed by sensory axons during developmental stages, whereas most spinal cord neurons are negative for cGKI. Analysis of the trajectories of axons within the spinal cord showed a longitudinal guidance defect of sensory axons within the developing dorsal root entry zone in the absence of cGKI. Consequently, in cGKI-deficient mice, fewer axons grow within the dorsal funiculus of the spinal cord, and lamina-specific innervation, especially by nociceptive sensory neurons, is strongly reduced as deduced from anti-trkA staining. These axon guidance defects in cGKI-deficient mice lead to a substantial impairment in nociceptive flexion reflexes, shown using electrophysiology. In vitro studies revealed that activation of cGKI in embryonic dorsal root ganglia counteracts semaphorin 3A–induced growth cone collapse. Our studies therefore reveal that cGMP signaling is important for axonal growth in vivo and in vitro.

Non-anticoagulant functions of heparin and heparan sulfate

1996 ◽  
Vol 16 (01) ◽  
pp. 6-14 ◽  
Author(s):  
E. Buddecke
Keyword(s):  
Extracellular Matrix ◽  
Cell Surface ◽  
Heparan Sulfate ◽  
Structural Features ◽  
Coat Proteins ◽  
Antiproliferative Effects ◽  
Viral Coat ◽  
Adhesive Proteins

SummaryHeparin is known to bind a large number of proteins not involved in anticoagula-tion, such as growth factors, adhesive proteins of the extracellular matrix, viral coat proteins and other enzymes and proteins. In vivo predominantly heparan sulfate – the most ubiquitous cell surface glycosaminoglycan – takes the functional role of heparin. Structural features, sources and non-anticoagulant func-tions of heparin and heparan sulfate proteoglycan are described. The functional diversity of heparin and heparan sulfate is reviewed in the following sections: (I) heparin and heparan sulfate as partners in fibroblast growth factor action, (II) antiproliferative effects of heparan sulfate and heparin, (III) cell surface heparan sulfate as extracellular matrix receptor and coreceptor, (IV) proteoheparan sulfate in central and peripheral nervous system, (V) role of proteoheparan sulfate in binding and uptake of lipoproteins, (VI) virus and spirochete binding to heparin and heparan sulfate.

scholarly journals Upregulation of EMMPRIN (OX47) in Rat Dorsal Root Ganglion Contributes to the Development of Mechanical Allodynia after Nerve Injury

2015 ◽  
Vol 2015 ◽  
pp. 1-9 ◽  
Author(s):  
Qun Wang ◽  
Yanyuan Sun ◽  
Yingna Ren ◽  
Yandong Gao ◽  
Li Tian ◽  
...  
Keyword(s):  
Extracellular Matrix ◽  
Neuropathic Pain ◽  
Dorsal Root Ganglion ◽  
Nerve Injury ◽  
Messenger Rna ◽  
Dorsal Root ◽  
Mechanical Allodynia ◽  
Cellular Localization ◽  
Altered Expression

Matrix metalloproteinases (MMPs) are widely implicated in inflammation and tissue remodeling associated with various neurodegenerative diseases and play an important role in nociception and allodynia. Extracellular Matrix Metalloproteinase Inducer (EMMPRIN) plays a key regulatory role for MMP activities. However, the role of EMMPRIN in the development of neuropathic pain is not clear. Western blotting, real-time quantitative RT-PCR (qRT-PCR), and immunofluorescence were performed to determine the changes of messenger RNA and protein of EMMPRIN/OX47 and their cellular localization in the rat dorsal root ganglion (DRG) after nerve injury. Paw withdrawal threshold test was examined to evaluate the pain behavior in spinal nerve ligation (SNL) model. The lentivirus containing OX47 shRNA was injected into the DRG one day before SNL. The expression level of both mRNA and protein of OX47 was markedly upregulated in ipsilateral DRG after SNL. OX47 was mainly expressed in the extracellular matrix of DRG. Administration of shRNA targeted against OX47 in vivo remarkably attenuated mechanical allodynia induced by SNL. In conclusion, peripheral nerve injury induced upregulation of OX47 in the extracellular matrix of DRG. RNA interference against OX47 significantly suppressed the expression of OX47 mRNA and the development of mechanical allodynia. The altered expression of OX47 may contribute to the development of neuropathic pain after nerve injury.

Sign in / Sign up

Export Citation Format

Share Document