The cells of all mammalian organs are connected by groups of cell-to-cell channels called gap junctions. To understand these functions one must first understand the physiological requirements of the lens. We therefore UR-144 first review the development and structure of the lens its numerous transport systems how these systems are integrated to generate the lens circulation the roles of the circulation in lens homeostasis and finally the functions of lens connexins in growth development and the lens circulation. I. INTRODUCTION A. Gap Junctions Gap junctional communication is required for physiological processes such as cell synchronization differentiation growth and metabolic coordination (143 217 Gap junctions facilitate these processes by providing a pathway for the intercellular exchange of ions (Na+ K+ Ca2+ Cl?) second messengers [cAMP cGMP inositol trisphosphate (IP3)] and small metabolites (glucose amino acids) allowing both electrical and biochemical coupling between cells (74 89 Gap junctions are highly specialized clusters of intercellular channels that form where the membranes of two neighboring cells are closely apposed (28) leaving a 2-nm gap for which gap junctions were originally named (170). In chordates the connexin family of genes (abbreviated Cx) encodes the vast majority of the space junction proteins (217 218 Recently another group of putative space junction proteins called pannexins (abbreviated Panx) have been identified and have been UR-144 shown to be expressed in various vertebrate tissues including the lens (12 56 153 Although one pannexin protein (Panx1) has been shown to form space junction channels in vitro (27) it’s been recommended that their main physiological function in vivo could be the forming of nonjunctional membrane stations connected with ATP and Ca2+ signaling (43 93 159 160 179 198 205 To time just the connexins have already been unambiguously defined as bona fide difference junction proteins in the zoom lens and we’ll limit our debate right here to connexin-mediated junctional conversation. Connexins possess four transmembrane domains developing the route wall structure/pore. These domains are linked by two extracellular loops that regulate cell-cell identification and docking procedures and prolong the wall structure/pore over the extracellular difference. Connexin proteins likewise have cytoplasmic NH2 and COOH termini and a cytoplasmic loop linking the next and third transmembrane domains (230). The transmembrane domains NH2 terminus and extracellular loops are extremely conserved among different connexin proteins as the series and amount of both cytoplasmic loop and COOH terminus are extremely adjustable (213). The cytoplasmic tail and loop are available to posttranslational adjustments that are thought to enjoy regulatory assignments (41). Every one of the zoom lens connexins are phosphoproteins (99 148 203 and phosphorylation is certainly regarded as very important to the legislation of set up and modulation UR-144 from the physiological properties from the stations (102 108 Six connexin protein oligomerize to create hemichannels (also known as connexons) which in turn are transported towards the plasma membrane. Hemichannnels from two adjacent cells align with one another in the UR-144 extracellular space to comprehensive the forming of a cell-to-cell route (89). Hemichannels could be produced either from an individual kind of connexin or from several type resulting in the creation of either homomeric or Rabbit Polyclonal to FOXH1. heteromeric hemichannels UR-144 respectively (Fig. 1). Extra complexity can be done during the development of the difference junctional stations. Adjacent cells can lead various kinds of hemichannels developing homotypic (association of two similar homomeric hemichannels) heterotypic (mix of two homomeric hemichannels each of different connexin origins) or heteromeric stations (comprising 2 distinctive heteromeric hemichannels). The forming of these structures depends upon the compatibility of connexins developing the stations rather than all connexins can connect to each other. For instance Cx43 was proven to type heterotypic stations with Cx50 however not with Cx46 an activity of selective compatibility that’s regulated with the sequences from the extracellular loops (214). These complicated interactions raise the structural and useful variety of junctional conversation allowing a huge array of opportunities in the properties of coupling between cells. Fig. 1 The nomenclature for the various types of intercellular stations that can type a.