Connexins and Integrins in Exosomes

Abstract

Connexins and integrins, the two structurally and functionally distinct families of transmembrane proteins, have been shown to be inter-connected by various modes of cross-talk in cells, such as direct physical coupling via lateral contact, indirect physical coupling via actin and actin-binding proteins, and functional coupling via signaling cascades. This connexin-integrin cross-talk exemplifies a biologically important collaboration between channels and adhesion receptors in cells. Exosomes are biological lipid-bilayer nanoparticles secreted from virtually all cells via endosomal pathways into the extracellular space, thereby mediating intercellular communications across a broad range of health and diseases, including cancer progression and metastasis, infection and inflammation, and metabolic deregulation. Connexins and integrins are embedded in the exosomal membranes and have emerged as critical regulators of intercellular communication. This concise review article will explain and discuss recent progress in better understanding the roles of connexins, integrins, and their cross-talk in cells and exosomes.

Targeted remodeling of breast cancer and immune cell homing niches by exosomal integrins

“…Exosomes are lipid bilayer biological nanoparticles that are generated by the cellular endosomal pathway and which are secreted to extracellular spaces. As exosomes encapsulate microRNAs, enzymes and mediators, they act as an important means of intercellular communication between not only neighboring cells via local diffusion, but also between distant cells via systemic dissemination through the blood circulation [5,6] (Fig. 1).…”

“…Further investigations are needed to aid the development of novel therapeutic approaches geared towards interfering with exosomal integrins. By this means, inflammation in cell micro-environments can be alleviated and physiologic tissue homeostasis restored [5,6].…”

Physiologic constraints of using exosomes in vivo as systemic delivery vehicles

“…(17,22,102) Which types of recipient cells are using these mechanisms is not well delineated. If receptor-mediated endocytosis renders the specificity of the interaction between exosome and recipient cell, cell adhesion molecules will be involved (103)(104)(105)(106)(107)(108)(109)(110). Among four groups of cell adhesion molecules (CAMs) of immunoglobulin (Ig) superfamily, cadherin, integrin and C-type lectin-domain proteins (CTLD), integrins received attention as the first paper of organotropism reported that the formation of premetastatic niche was made possible by delivery of exosomes having α6β4 (for laminin) and α6β1 to the lungs and αvβ5 (for vitronectin) for the liver (111) ( Figure 8A).…”

“…Undoubtedly, the mechanism of recognition of the exosomes by the recipient cells depends upon the surface characteristics of exosomes. (17,22,102,107) While we think about the diversity of receptors of the recipient cells, such as Ig superfamily, endocytosis-prone receptors for ligands, scavenger receptor, peptidoglycan or sphingomyelins and the similar, positioning the surface molecules inappropriate amount at correct loci along the membranes would be important. If bioengineering is planned, investigators need to characterize the factors and then modify the relevant molecules by inserting, deleting, or removing them.…”

“…The recipient cells would have specific receptors such as neural CAM (NCAM), adherin, selectin and immunoglobulin superfamily (IgSF), intercellular adhesion molecule (ICAM) and yet-to-be found many adhesion molecules. (68,101,107) Neurotransmitters of small molecules or small peptides transmit the information between neurons and astrocytes. Synaptic cleft and neuron-astrocyte couples have been keeping and exchanging these transmitters around the close vicinity.…”