scholarly journals Thrombospondin-1 Promotes Circuit-Specific Synapse Formation via β1-Integrin

2019 ◽  
Author(s):  
Sehwon Koh ◽  
Suva Roy ◽  
Oznur Eroglu ◽  
Samuel Strader ◽  
William J. Chen ◽  
...  
Keyword(s):  
Glial Cells ◽  
Synapse Formation ◽  
Excitatory Synapse ◽  
Synaptic Connectivity ◽  
Β1 Integrin ◽  
Laminar Organization ◽  
Synaptic Circuits ◽  
Conditional Deletion ◽  
Subtype Specificity ◽  
Thrombospondin 1

SUMMARYGlial cells regulate synaptic connectivity during development, but whether they selectively instruct the formation of specific synaptic circuits is not known. Here we show that the major perisynaptic glia of the retina, the Muller glia (MG), control the proper establishment of the direction-selective (DS) circuit by a synaptogenic protein, Thrombospondin 1 (TSP1). We found that TSP1 promotes excitatory synapse formation specifically in on-off Direction-Selective retinal Ganglion Cells (ooDSGCs). Lack of TSP1 leads to reduced synapse formation within the inner plexiform sublayers containing DS-circuit, resulting in deficits of ooDSGC function. Even though pan-TSP receptor, α2δ-1, interaction is required for TSP1-induced synapse formation, the ooDSGC-subtype specificity of TSP1 is conferred by a second neuronal TSP1 receptor, β1-Integrin. Furthermore, conditional deletion of β1-Integrin in ooDSGCs results in diminished excitatory synapse formation without disturbing laminar organization showing that MG-secreted TSP1 controls circuit-specific synapse formation via β1-Integrin.

scholarly journals Thrombospondin-1 Promotes Circuit-Specific Synapse Formation Via β1-Integrin

2019 ◽  
Author(s):  
Sehwon Koh ◽  
Suva Roy ◽  
Oznur Eroglu ◽  
Samuel Strader ◽  
William J. Chen ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Β1 Integrin ◽  
Thrombospondin 1

scholarly journals Neuron-Glia Interactions in Neurodevelopmental Disorders

Cells ◽  
2020 ◽  
Vol 9 (10) ◽  
pp. 2176 ◽  
Author(s):  
Yoo Sung Kim ◽  
Juwon Choi ◽  
Bo-Eun Yoon
Keyword(s):  
Glial Cells ◽  
Neurodevelopmental Disorders ◽  
Synapse Formation ◽  
Physiological Function ◽  
Anion Channel ◽  
Synaptic Dysfunction ◽  
Synaptic Homeostasis ◽  
The Central Nervous System ◽  
Gap Junction Hemichannel ◽  
Novel Therapeutic

Recent studies have revealed synaptic dysfunction to be a hallmark of various psychiatric diseases, and that glial cells participate in synapse formation, development, and plasticity. Glial cells contribute to neuroinflammation and synaptic homeostasis, the latter being essential for maintaining the physiological function of the central nervous system (CNS). In particular, glial cells undergo gliotransmission and regulate neuronal activity in tripartite synapses via ion channels (gap junction hemichannel, volume regulated anion channel, and bestrophin-1), receptors (for neurotransmitters and cytokines), or transporters (GLT-1, GLAST, and GATs) that are expressed on glial cell membranes. In this review, we propose that dysfunction in neuron-glia interactions may contribute to the pathogenesis of neurodevelopmental disorders. Understanding the mechanisms of neuron-glia interaction for synapse formation and maturation will contribute to the development of novel therapeutic targets of neurodevelopmental disorders.

scholarly journals Thrombospondin-1 in maladaptive aging responses: a concept whose time has come

2020 ◽  
Vol 319 (1) ◽  
pp. C45-C63
Author(s):  
Jeffrey S. Isenberg ◽  
David D. Roberts
Keyword(s):  
Molecular Mechanisms ◽  
Synapse Formation ◽  
Genotoxic Stress ◽  
Cell Types ◽  
Cellular Tissue ◽  
Therapeutic Agents ◽  
Age Related ◽  
Organ Systems ◽  
Age Dependent ◽  
Thrombospondin 1

Numerous age-dependent alterations at the molecular, cellular, tissue and organ systems levels underlie the pathophysiology of aging. Herein, the focus is upon the secreted protein thrombospondin-1 (TSP1) as a promoter of aging and age-related diseases. TSP1 has several physiological functions in youth, including promoting neural synapse formation, mediating responses to ischemic and genotoxic stress, minimizing hemorrhage, limiting angiogenesis, and supporting wound healing. These acute functions of TSP1 generally require only transient expression of the protein. However, accumulating basic and clinical data reinforce the view that chronic diseases of aging are associated with accumulation of TSP1 in the extracellular matrix, which is a significant maladaptive contributor to the aging process. Identification of the relevant cell types that chronically produce and respond to TSP1 and the molecular mechanisms that mediate the resulting maladaptive responses could direct the development of therapeutic agents to delay or revert age-associated maladies.

scholarly journals EphB Receptors Interact with NMDA Receptors and Regulate Excitatory Synapse Formation

Cell ◽  
2000 ◽  
Vol 103 (6) ◽  
pp. 945-956 ◽  
Author(s):  
Matthew B Dalva ◽  
Mari A Takasu ◽  
Michael Z Lin ◽  
Steven M Shamah ◽  
Linda Hu ◽  
...  
Keyword(s):  
Nmda Receptors ◽  
Synapse Formation ◽  
Excitatory Synapse ◽  
Ephb Receptors

scholarly journals EphB-Mediated Degradation of the RhoA GEF Ephexin5 Relieves a Developmental Brake on Excitatory Synapse Formation

Cell ◽  
2010 ◽  
Vol 143 (3) ◽  
pp. 442-455 ◽  
Author(s):  
Seth S. Margolis ◽  
John Salogiannis ◽  
David M. Lipton ◽  
Caleigh Mandel-Brehm ◽  
Zachary P. Wills ◽  
...  
Keyword(s):  
Synapse Formation ◽  
Excitatory Synapse

scholarly journals Netrin Participates in the Development of Retinotectal Synaptic Connectivity by Modulating Axon Arborization and Synapse Formation in the Developing Brain

2009 ◽  
Vol 29 (36) ◽  
pp. 11065-11077 ◽  
Author(s):  
C. Manitt ◽  
A. M. Nikolakopoulou ◽  
D. R. Almario ◽  
S. A. Nguyen ◽  
S. Cohen-Cory
Keyword(s):  
Synapse Formation ◽  
Developing Brain ◽  
Synaptic Connectivity
Sign in / Sign up

Export Citation Format

Share Document