Cytoplasmic region

In this lecture we will be concerned by exocytosis of neurotransmitters by chromaffin cells. These cells, located above kidneys, produce the adrenaline burst which induces fast body reactions they are used in neurosciences as standard models for the study of exocytosis by catecholaminergic neurons. Prior to exocytosis, adrenaline is contained at highly concentrated solutions into a polyelectrolyte gel matrix packed into small vesicles present in the cell cytoplasm and brought by the cytoskeleton near the cell outer membrane. Stimulation of the cell by divalent ions induces the fusion of the vesicles membrane with that of the cell and hence the release of the intravesicular content into the outer-cytoplasmic region. 

Thyrotropin (TSH) regulates the production and secretion of thyroid hormones as well as thyroid epithelial cell growth via the TSH receptor. The TSH receptor belongs to the family of G protein-coupled receptors. It is composed of 764 amino acids. The receptor contains a long hydrophilic region orientated towards the exterior of the cell (ectodomain), 7 hydrophobic transmembrane domains and a short cytoplasmic region. 

FERM 4.1/ezrin/radixin/moesin domain Binding to cytoplasmic regions of transmembrane proteins... 

NPQ (Rakhimberdieva et al. 2004) exactly matches the absorption spectrum of the carotenoid, 3 -hydrox yech i nenone (Polivka et al. 2005) in the OCP. The OCP is now known to be specifically involved in the phycobilisome-associated NPQ and not in other mechanisms affecting the levels of fluorescence such as state transitions or D1 damage (Wilson et al. 2006). Studies by immunogold labeling and electron microscopy showed that most of the OCP is present in the interthylakoid cytoplasmic region, on the phycobilisome side of the membrane, Figure 1.2 (Wilson et al. 2006). The existence of an interaction between the OCP and the phycobilisomes and thylakoids was supported by the co-isolation of the OCP with the phycobilisome-associated membrane fraction (Wilson et al. 2006, 2007). 

Figure 10.7 The EGF receptor. The N-terminal, extracellular region of the receptor contains 622 amino acids. It displays two cysteine-rich regions, between which the ligand-binding domain is located. A 23 amino acid hydrophobic domain spans the plasma membrane. The receptor cytoplasmic region contains some 542 amino acids. It displays a tyrosine kinase domain, which includes several tyrosine autophosphorylation sites, and an actin-binding domain that may facilitate interaction with the cell cytoskeleton...

As mentioned above, the junctional SR is connected to sheets of perpendicular SR (Fig. 4), which extend from the PM through a peripheral cytoplasmic region with lower myofilament density into the myoplasm. It is proposed that during the active state of wave-like [Ca2+]j oscillations, Ca2+ taken up by the junctional SR is released by these perpendicular sheets near the calmodulin, which is tethered to the myosin light chain kinase (MLCK) of the thin filaments (M. Walsh, personal communication, 2001). This process would enhance the specificity and efficiency of Ca2+ regulation of contraction. 

FcyRIIB generates three transcripts from alternative splicing of exons encoding either the cytoplasmic region (transcripts bl, b2) or the signal sequence (b3). 

The closely related Trk B serves as a receptor for BDNF. Two variants of this glycoprotein have been characterized a larger (145 kDa) form and a truncated (95 kDa) form. While exhibiting identical extracellular domains, the 95 kDa protein has a short (23 amino acid) cytoplasmic region, whereas the 145 kDa form displays a larger (tyrosine kinase) cytoplasmic domain. Trk B also serves as a functional receptor for NT-3 and NT-4/5 and is expressed widely throughout the central and peripheral nervous system. 

The T cell receptors (see Chapter 11) are an example of receptors composed of several subimits. Ligand binding to the receptor activates an associated tyrosine kinase which phosphorylates Tyr residues in the cytoplasmic region of the receptor and thus creates binding sites for SH2 domains of effector molecules downstream. 

The receptor-like protein tyrosine phosphatases have a transmembrane and, in some cases, a large extracellular domain with a very variable structme (Fig. 8.16). Many, but not all, membrane protein tyrosine phosphatases have two catalytic domains in the cytoplasmic region. The complete structme is very similar to the structure of transmembrane receptors. Understanding of their function is far from complete. Both the natural ligands and the substrate proteins following in the sequence are incompletely characterized. Several studies have demonstrated a role for receptor-like PTPs in neuronal cell adhesion signaling pathways. In cells of the neural tissue, a surface protein, contactin has been identified as ligand for the extracellular domain of a protein tyrosine phosphatase (Peles et al., 1995). 

Like many other ligand-gated ion chaimels, the charmel gating properties of the NMDA receptor are regulated by phosphorylation. The NR2 subimit of the receptor contains many Tyr phosphorylation sites in the cytoplasmic region and it has been shown that receptor activity is stimulated by Tyr phosphorylation. Cytoplasmic nonreceptor tyrosine kinases of the Src family are responsible for the Tyr phosphorylation. Thus, a specific association with PSD-95, and thereby mediation of phosphorylation of NR2, has been demonstrated for the Fyn kinase, a member of the Src kinase family (Tezuka et al., 1999). Thus, the nonreceptor tyrosine kinase has an important role in regulation of synaptic activity and plasticity. A model for Fyn association with the NMDA receptor/PSD95 complex is shown in Fig. 16.11. 

Fig. 16.13. Pore structure of the acetylcholine receptor, based on electron microscopy studies. a) Electron density map of the acetylcholine receptor of the postsynaptic membrane of the electric organ of the ray Torpedo californicus, based on electron microscopy studies. The receptor has a long funnel-like structure in the extracellular region, which narrows at the center of the pore. A smaller funnel structure is observed in the cytoplasmic region of the receptor. Another protein is situated on the cytoplasmic side. The long arrow indicates the direction of ion passage and the small arrow shows the postulated binding site for acetylcholine, b) Schematic representation of the acetylcholine receptor with the M2 hehx as the central block in the ion channel. According to Unwin, (1993).

Sato N, Sakamaki K, Terada N, Arai K, Miyajima A. 1993. Signal transduction by the high-affinity GM-CSF receptor Two distinct cytoplasmic regions of the common beta subunit responsible for different signaling. EMBO J. 12 4181—4189. 

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