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The "secretory" Na+-K+-2Cl- cotransporter, NKCC1, is a member of a small gene family of electroneutral cation-chloride cotransporters (CCCs) with 9 homologues in vertebrates. A number of these transporters, including NKCC1 itself, have been shown to exist as homodimers in the membrane, suggesting that this may be a common feature of the CCCs. Here we employ(More)
Nicotine alters a broad spectrum of behaviors, including attention, arousal, anxiety, and memory. The cellular physiology of nicotine is comparably diverse: nicotine interacts with an array of ionotropic receptors whose gating can lead to direct depolarization of neurons or to an indirect modulation of neuronal excitability by presynaptic facilitation.(More)
Mutations of human presenilin 1 (PS1) have been genetically linked to early-onset familial Alzheimer's disease. PS1 contains 10 hydrophobic regions (HRs) sufficiently long to be alpha-helical membrane spanning segments. Most previous topology studies agree that the N-terminus of PS1 is cytosolic and HRs 1-6 span the membrane but HR 7 does not. However,(More)
The TRPC ion channels are candidates for the store-operated Ca(2+) entry pathway activated in response to depletion of intracellular Ca(2+) stores. Hydropathy analyses indicate that these proteins contain eight hydrophobic regions (HRs) that could potentially form alpha-helical membrane-spanning segments. Based on limited sequence similarities to other ion(More)
The molecular mechanisms of the nonamyloidogenic and the amyloidogenic pathways of the amyloid precursor protein (APP) are unknown, but proteolysis of APP is essential for the generation of beta-amyloid. To study the time-course of C-terminal fragment generation by alpha- and beta-secretase, we expressed the APP751 isoform with the Swedish mutation in the(More)
The polytopic membrane protein presenilin 1 (PS1) is a component of the gamma-secretase complex that is responsible for the intramembranous cleavage of several type I transmembrane proteins, including the beta-amyloid precursor protein (APP). Mutations of PS1, apparently leading to aberrant processing of APP, have been genetically linked to early-onset(More)
The "secretory" Na+-K+-2Cl- cotransporter (NKCC1) is a member of a small gene family with nine homologues in vertebrates. Of these, seven are known to be electroneutral chloride transporters. These transporters play a number of important physiological roles related to salt and water homeostasis and the control of intracellular chloride levels. Hydropathy(More)
Interactions between abnormal amyloid precursor protein metabolism and cholinergic dysfunction are increasingly apparent. Both of these major features of Alzheimer's disease occur in restricted loci in normal aging--a potential model for early Alzheimer type pathology. Entorhinal cortex is particularly vulnerable to beta-amyloidosis and compared with other(More)
The membrane-bound protein complex gamma-secretase is an intramembranous protease whose substrates are a number of type I transmembrane proteins including the beta-amyloid precursor protein (APP). A presenilin molecule is thought to be the catalytic unit of gamma-secretase and either of two presenilin homologues, PS1 or PS2, can play this role. Mutations in(More)
Monoclonal antibodies directed against antigens in the apical plasma membrane of the toad kidney epithelial cell line A6 were produced to probe the phenomena that underlie the genesis and maintenance of epithelial polarity. Two of these antibodies, 17D7 and 18C3, were selected for detailed study here. 17D7 is directed against a 23-kD peptide found on both(More)
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