Gap junction modulation by extracellular signaling molecules: the thymus model

Abstract

Gap junctions are intercellular channels which connect adjacent cells and allow direct exchange of molecules of low molecular weight between them. Such a communication has been described as fundamental in many systems due to its importance in coordination, proliferation and differentiation. Recently, it has been shown that gap junctional intercellular communication (GJIC) can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances. Herein, we discuss some aspects of the general modulation of GJIC by extracellular messenger molecules and more particularly the regulation of such communication in the thymus gland. Additionally, we discuss recent data concerning the study of different neuropeptides and hormones in the modulation of GJIC in thymic epithelial cells. We also suggest that the thymus may be viewed as a model to study the modulation of gap junction communication by different extracellular messengers involved in non-classical circuits, since this organ is under bidirectional neuroimmunoendocrine control.

Fibroblast-like synoviocyte mechanosensitivity to fluid shear is modulated by interleukin-1α

“…Specifically, the glycocalyx has been shown to play a role in mechanosensing of smooth muscle cells and fibroblasts of the vascular system (Ainslie, Garanich et al 2005, Tarbell and Pahakis 2006, Shi and Tarbell 2011), and may be a relevant mechanism in the synovium during OA as changes occur to the interstitial matrix. Other work investigating the mechanisms addressed in this study already provide examples of potential strategies for controlling mechanosensitivity, such as manipulation of primary cilia length (Ou, Ruan et al 2009, Besschetnova, Kolpakova-Hart et al 2010) and gap junctional communication (Alves, Nihei et al 2000, Kurtenbach and Zoidl 2014). As such, we anticipate that a better understanding of these mechanisms will not only shed light on how the pathological sensitization of FLS to shear stress observed here contributes to the pathophysiology of OA, but point to therapeutic interventions that restore normal mechanosensitivity and hinder progression of the disease.…”

Gap junction-mediated antigen transport in immune responses

“…Several studies have indicated the involvement of gap junctions in the communication between cells of the immune system [17][18][19][20][21][22][23][24]. Indirect evidence for the importance of gap junctions in immunity comes from the observation that viruses -such as herpes simplex virus (HSV) and human papillomavirus (HPV) -actively influence gap junction communication [25][26][27][28].…”

Alterations in metabolism and gap junction expression may determine the role of astrocytes as “good samaritans” or executioners

“…Gap junctional intercellular communication can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors and some paracrine substances (Alves et al, 2000a). Activation of either voltage-or receptor-operated channels may modulate function of gap junctions and therefore transfer of signaling molecules through them.…”

“…Recent work suggests that there is not an easy answer to the questions of whether gap junctions can be mediators/ wave via gap junctional intercellular communication (GJIC) forms the spreading depression leading to the expansion of stroke volume. Gap junctional intercellular communication can be modulated by several extracellular soluble factors such as classical hormones, neurotransmitters, interleukins, growth factors, and some paracrine substances (Alves et al, 2000a). Activation of either voltage-gated channels or receptor-operated channels (e.g., glutamate) may modulate function of gap junctions and therefore transfer of signaling molecules through them.…”