Differential isoform localization

Usuda, N., Arai, H., Sasaki, H., Hanai, T., Nagat, T., Muramatsu, T., Kincaid, R. L., and Higuchi, S. 1996. Differential subcellular localization of neural isoforms of the catalytic subunit of calmodulin dependent protein phosphatase (calcineurin) in central nervous system neurons Immunohistochemistry on formalin-fixed paraffin sections employing antigen retrieval by microwave irradiation. J. Histochem. Cytochem. 44 13-18. 

Baines, I.C., Brzeska, H., Korn, E.D. (1992). Differential localization of Acanthamoeba myosin I isoforms. J. Cell Biol. 119. 1193-1203. 

Despite the similar functions of each isozyme, only two regions of amino acid homology exist (X and Y), one of 150 and a second of 120 amino acid residues, which are 54% and 42% identical among the isozymes but are differentially localized within each enzyme (Fig. 20-3). The X and Y domains form the catalytic core of the enzyme. A characteristic of the (3 and 8 isoforms is that relatively few amino acids (40-110) separate the X and Y entities, whereas a much larger separation is observed for the PLCy isoform (approx. 400). In addition, in PLCy, the region between X and Y contains amino acid sequences that are found in nonreceptor tyrosine kinases (SH2 and SH3 domains). All four isoforms possess pleckstrin homology (PH) domains. The latter are considered to enable the enzyme to become tethered to the plasmalemma via an interaction with PI(4,5)P2. In addition, all PLC isoforms possess an E-F hand domain, which is located between PH and X domains, and a C2 domain, which is located close to the Y domain. 

The ultimate localization of LC depends on toxin type, with, for example, type A residing near the plasma membrane and type E remaining in the cytosol, a phenomenon that may explain the differential stability of the toxin isoforms and the persistence of their action. Nevertheless, the LC fragment is always effectively sequestered from the degradative cycle of the terminal. Tyrosines in both LC and HC may be phosphorylated by Src (see Ch. 24), enhancing the stability and proteolytic activity of LC. 

Differential effects of the isoforms of a particular factor could be the consequence of receptor-mediated signaling. Proliferation leading to selfrenewal could depend on the signaling intensity through the factor/receptor complex (Zandstra et al., 2000). In this context, membrane-bound factors mediating cell-cell interactions may substitute for high local concentrations of a soluble factor resulting in delayed internalization of the factor/receptor complex... 

G protein j3y-subunit <1, 3, 4> (<3> lOfold activation, /f-ARK 1 and 2, increases incorporation of phosphate from 4 to 10 mol phosphate/mol receptor [13] <3> activates, binding domain is localized to the C-terminal region of j3-ARK [15,17,28] <3> from brain, binds to the C-terminal half of the PH domain [17] <3> from bovine brain, -ARK 1 and 2 requirement, selectivity for Py subunits, both isoforms differentiate between defined Py subunits [24] <3> requirement, binding plays an important role in specifically targeting the enzyme complex to its receptor substrate [25] <4> from brain, stimulates the phosphorylation of rhodopsin, but not of the peptide RRREEEEESAAA,... 

The 5-HT2C receptors are considered to be restricted to the CNS (139), where they are edited in many isoforms (at least 14) that appear to be differentially distributed (e.g., refs. 140-142). In this context, antibodies specifically directed againt these isoforms could, in principle, allow one to determine their respective or common cellular and subcellular localization. However, the two antibodies available to date (73,143) are directed against the C-terminal portion, a region not affected by the editing. 

Louneva N, Talbot K, Cox M, Han L-Y, Blake DJ, et al. 2007 Dysbindin-1 isoforms are differentially localized in pre-and post-synaptic fractions of the mouse brain. (Abstract 59.7 from 2007 Society for Neuroscience Annual Meeting, San Diego, CA). 

Smooth and nonmuscle myosin rods terminate in a nonhelical tailpiece that is not present in sarcomeric muscle myosins. Two different-length isoforms of this tailpiece have been identified (SMI and SM2). Since the strongest interactions necessary for assembly have been localized to the C terminus of the rod, there have been suggestions that the two tailpieces may differentially influence filament stability or packing. Moreover, some smooth muscle myosins, such as that from aorta, contain a serine residue in the nonhelical tailpiece that can be phosphorylated in cells by casein kinase II (Kelley and Adelstein, 1990). This site is present only in the longer of the two tailpieces, and it is notably absent from gizzard myosin, where the homologous phosphorylatable Ser residue is Gly. 

PKA diversity lies in both its R and C subunits. Molecular cloning has revealed a and [3 isoforms of both the classically described PKA regulatory subunits (RI and RII), as well as three C subunit isoforms Ca, Cfi, and Cy. The R subunits exhibit different binding affinities for cyclic AMP giving rise to PKA holoenzymes with different thresholds for activation. In addition to differential expression of R and C isoforms in various cells and tissues, PKA function is modulated by subcellular localization mediated by A-kinase-anchoring proteins (AKAPs). 

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