Cellular vesicular processes

The epithelial membrane of the GI tract consists of a continuous barrier of cells, which allows the transport of low-molecular-weight molecules by simple diffusion or various carrier processes. Macromolecules such as proteins may be absorbed from the intestinal lumen by cellular vesicular processes, through fluid-phase endocytosis (pinocytosis), or by receptor-mediated endocytosis or transcytosis (Fig. 6). In pinocytosis, extracellular fluid is captured within an epithelial membrane vesicle. It begins with the formation of a pocket... 

Two mechanisms have been proposed to explain the transport of phospholipids from the ER to other cellular membranes protein-mediated transfer and a vesicular process. Several experiments have demonstrated that water-soluble proteins, known as phospholipid exchange proteins, can bind to specific phospholipid molecules and transfer them to another bilayer. Vesicular transport of phospholipids and membrane proteins in structures known as transition vesicles from the ER to the Golgi complex is not clearly understood. However, evidence of transfer of luminal material from the ER to the Golgi cistemae clearly supports vesicular transport. 

Vesicular proteins and lipids that are destined for the plasma membrane leave the TGN sorting station continuously. Incorporation into the plasma membrane is typically targeted to a particular membrane domain (dendrite, axon, presynaptic, postsynaptic membrane, etc.) but may or may not be triggered by extracellular stimuli. Exocytosis is the eukaryotic cellular process defined as the fusion of the vesicular membrane with the plasma membrane, leading to continuity between the intravesicular space and the extracellular space. Exocytosis carries out two main functions it provides membrane proteins and lipids from the vesicle membrane to the plasma membrane and releases the soluble contents of the lumen (proteins, peptides, etc.) to the extracellular milieu. Historically, exocytosis has been subdivided into constitutive and regulated (Fig. 9-6), where release of classical neurotransmitters at the synaptic terminal is a special case of regulated secretion [54]. 

The cytosol is the fluid compartment of the cell and contains the enzymes responsible for cellular metabolism together with free ribosomes concerned with local protein synthesis. In addition to these structures which are common to all cell types, the neuron also contains specific organelles which are unique to the nervous system. For example, the neuronal skeleton is responsible for monitoring the shape of the neuron. This is composed of several fibrous proteins that strengthen the axonal process and provide a structure for the location of specific membrane proteins. The axonal cytoskeleton has been divided into the internal cytoskeleton, which consists of microtubules linked to filaments along the length of the axon, which provides a track for the movement of vesicular material by fast axonal transport, and the cortical cytoskeleton. 

Phosphatidylinositol 3,5-bisphosphate (PI-3,5-P2, 6) is the low abundance, newest member of PIPn family (33). It is involved in mediation of several cellular processes such as vacuolar homeostasis, membrane trafficking, and vesicular protein sorting (36, 38). The recently discovered PI-3,5-P2 effectors include a family of -propeller, epsin, and CHMP protein families (39). The importance of PI-3,5-P2 in human physiology is demonstrated by its role in insulin signaling, myotubular myopathy, and corneal dystrophy (38). 

Cellular transport primarily occurs with the help of (7.) ionic channels, (2.) carrier proteins, (S.) pumps, and (4.) vesicles. These transport processes may be in the form of active, passive or vesicular mechanisms. 

The actin cytoskcleton is one of the most fascinating cellular networks that mediates a variety of essential biological processes critical for the survival of the cell. Its dynamic properties provide the basic force for various processes like cell migration, endocytosis, vesicular trafficking and cytokinesis. In order to efficiently execute all these dynamic processes the differential reguladon and recruitment of a plethora of actin-bindingproteins with distinctive activities is required. One of the major actin binding proteins that has been extensively studied in recent years is coronin. 

Cu is normally found at relatively high levels in the brain (100-150 xM) with substantial variations at the cellular and subcellular level [55-57]. Ionic Cu is compartmentalized into a post-synaptic vesicle and released upon activation of the NMDA-R but not AMPA/kainate-type glutamate receptors [58]. The Menkes Cu7aATPase is the vesicular membrane Cu transporter, and upon NMDA-R activation, it traffics rapidly and reversibly to neuronal processes, independent of the intracellular Cu concentration [58]. Cu ions function to suppress NMDA activation and prevent excitotoxicity by catalyzing S-nitrosylation of specific cysteine residues on the extracellular domain of the NRl and NR2A subunits of the NMDA receptor [58]. The concentrations of Cu in the synaptic cleft can reach approximately 15 xM. Subsequently, Cu is cleared by uptake mechanisms from the synaptic cleft. Several studies have shown that Cu levels increase with age in the brains of mice [22-24]. 

Many other proteins closely related to ras are now known and are considered as members of the ras superfamily which numbers >100 members. Within this superfamily are several subgroups, with Ras being joined by the Ran/Rac, Ypt/Rab and Rho proteins. The cellular functions of these proteins are exceedingly diverse including such processes as vesicular trafficking, cytoskeletal control and NADPH oxidase function. Clearly, such important proteins have plant homologues which will be discussed later. 

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