Abstract
The integrin family is involved in various biological functions, including cell proliferation, differentiation and migration, and also in the pathogenesis of disease. Integrins are multifunctional receptors that exist as heterodimers composed of α and β subunits and bind to various ligands, including extracellular matrix (ECM) proteins; they are found in many animals, not only vertebrates (e.g., mouse, rat, and teleost fish), but also invertebrates (e.g., planarian flatworm, fruit fly, nematodes, and cephalopods), which are used for research on genetics and social behaviors or as models for human diseases. In the present paper, we describe the results of a phylogenetic tree analysis of the integrin family among these species. We summarize integrin signaling in teleost fish, which serves as an excellent model for the study of regenerative systems and possesses the ability for replacing missing tissues, especially in the central nervous system, which has not been demonstrated in mammals. In addition, functions of astrocytes and reactive astrocytes, which contain neuroprotective subpopulations that act in concert with the ECM proteins tenascin C and osteopontin via integrin are also reviewed. Drug development research using integrin as a therapeutic target could result in breakthroughs for the treatment of neurodegenerative diseases and brain injury in mammals.
Highlights
Integrins are multifunctional receptors mainly responsible for binding to extracellular matrix (ECM) proteins that mediate cell adhesion
Since astrocytes express integrins and are potentially involved in central nervous system (CNS) regeneration and development of neuroimmunological diseases, we focus on the role of astrocytes participating in the integrin signaling
The mechanism of T cell infiltration into the brain has not yet been elucidated, but recently, Zondler et al reported that melanoma cell adhesion molecule (MCAM) signaling via phosphorylated PLCγ1 induced intracellular signaling leading to β1 integrin activation on human memory T cells, resulting in increased brain T cell infiltration [72]
Summary
Integrins are multifunctional receptors mainly responsible for binding to extracellular matrix (ECM) proteins that mediate cell adhesion. The Drosophila melanogaster position-specific antigen (PS) was characterized as a heterodimeric complex that shared a common subunit All of these findings were reported between 1986 and 1987 [5,6,7]. In the mammalian CNS, astrocytes are among the most abundant of glial cells that maintain the physiological integrity of the blood brain barrier (BBB), and play roles in glucose sensing (so-called astrocyte-neuron lactate shuttle hypothesis), blood flow regulation, synaptic functioning at tripartite synapses, gliotransmission, etc. Since astrocytes express integrins and are potentially involved in CNS regeneration and development of neuroimmunological diseases, we focus on the role of astrocytes participating in the integrin signaling
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