Protein degradation: the ins and outs of the matter

In eukaryotic cells, nascent membrane or secretory proteins are translocated into the endoplasmic reticulum through the Sec61p translocation channel; recent evidence suggests that, if they fail to achieve a native conformation, they are translocated back into the cytosol by the same route and degraded by the proteasome.     

The ins and outs of a molecular chaperone machine

Genetic and biochemical work has highlighted the biological importance of the GroEL/GroES (Hsp60/Hsp10; cpn60/cpn10) chaperone machine in protein folding. GroEL's donut-shaped structure has attracted the attention of structural biologists because of its elegance as well as the secrets (substrates) it can hide. The recent determination of the GroES and GroEL/GroES structures provides a glimpse of their plasticity, revealing dramatic conformational changes that point to an elaborate mechanism, coupling ATP hydrolysis to substrate release by GroEL.     

Going the distance with auxin: unravelling the molecular basis of auxin transport

Auxin represents one of the most important classes of signalling molecules described in plants. Auxins regulate several fundamental cellular processes including division, elongation and differentiation. Indole-3-acetic acid (IAA), the principal form of auxin in higher plants, is first synthesized within young apical tissues, then conveyed to its basal target tissues by a specialized delivery system termed polar auxin transport. The polarity of IAA movement represents one of the most novel aspect of auxin signalling. IAA transport has been demonstrated to involve auxin influx and efflux carrier activities. The adoption of a mutational approach in the model plant Arabidopsis thaliana has led to the identification of a number of genes which encode components for, or regulate the activity of, the auxin transport machinery. This paper will review the advances being made in identifying and characterizing these auxin transport-related gene products and discuss their importance within the context of Arabidopsis development.     

Ins and outs of LFA-1

Leukocyte function-associated molecule 1 (LFA-1) is an integrin that plays a major role in the immune system. Recent findings demonstrate that LFA-1 has a two-way signaling function, mediating cell adhesion and stimulating intracellular processes at the same time. Here, Marijke Lub, Yvette van Kooyk and Carl Figdor discuss the 'inside-out' and 'outside-in' signaling properties of LFA-1, as a prototype leukocyte integrin, in normal and malignant T cells. They integrate data into a model that highlights the role of the cytoskeleton in the regulation of LFA-1.     

A mutation in protein phosphatase 2A regulatory subunit A affects auxin transport in Arabidopsis

The phytohormone auxin controls processes such as cell elongation, root hair development and root branching. Tropisms, growth curvatures triggered by gravity, light and touch, are also auxin-mediated responses. Auxin is synthesized in the shoot apex and transported through the stem, but the molecular mechanism of auxin transport is not well understood. Naphthylphthalamic acid (NPA) and other inhibitors of auxin transport block tropic curvature responses and inhibit root and shoot elongation. We have isolated a novel Arabidopsis thaliana mutant designated roots curl in NPA (rcn1). Mutant seedlings exhibit altered responses to NPA in root curling and hypocotyl elongation. Auxin efflux in mutant seedlings displays increased sensitivity to NPA. The rcn1 mutation was transferred-DNA (T-DNA) tagged and sequences flanking the T-DNA insert were cloned. Analysis of the RCN1 cDNA reveals that the T-DNA insertion disrupts a gene for the regulatory A subunit of protein phosphatase 2A (PP2A-A). The RCN1 gene rescues the rcn1 mutant phenotype and also complements the temperature-sensitive phenotype of the Saccharomyces cerevisiae PP2A-A mutation, tpd3-1. These data implicate protein phosphatase 2A in the regulation of auxin transport in Arabidopsis.     

EIR1, a root-specific protein involved in auxin transport, is required for gravitropism in Arabidopsis thaliana

The EIR1 gene of Arabidopsis is a member of a family of plant genes with similarities to bacterial membrane transporters. This gene is expressed only in the root, which is consistent with the phenotypes of the eir1 mutants-the roots are agravitropic and have a reduced sensitivity to ethylene. The roots of eir1 mutants are also insensitive to the excess auxin produced by alf1-1 and fail to induce an auxin-inducible gene in the expansion zone. Although they fail to respond to internally generated auxin, they respond normally to externally applied auxin. Expression of the EIR1 gene in Saccharomyces cerevisiae confers resistance to fluorinated indolic compounds. Taken together, these data suggest that the EIR1 protein has a root-specific role in the transport of auxin.     

Nucleocytoplasmic transport: driving and directing transport

Nucleocytoplasmic transport involves assembly and movement across the nuclear envelope of cargo-receptor complexes that interact with the small GTPase Ran. The asymmetric distribution of Ran regulator proteins, RanGAP1 and RCC1, provides the driving force and directionality for nuclear transport.     

The amino acid/auxin:proton symport permease family

Amino acids and their derivatives are transported into and out of cells by a variety of permease types which comprise several distinct protein families. We here present a systematic analysis of a group of homologous transport proteins which together comprise the eukaryotic-specific amino acid/auxin permease (AAAP) family (TC #2. 18). In characterizing this family, we have (1) identified all sequenced members of the family, (2) aligned their sequences, (3) identified regions of striking conservation, (4) derived a family-specific signature sequence, and (5) proposed a topological model that appears to be applicable to all members of the family. We have also constructed AAAP family phylogenetic trees and dendrograms using six different programs that allow us to trace the evolutionary history of the family, estimate the relatedness of proteins from dissimilar organismal phyla, and evaluate the reliability of the different programs available for phylogenetic studies. The TREE and neighbor-joining programs gave fully consistent results while CLUSTAL W gave similar but non-identical results. Other programs gave less consistent results. The phylogenetic analyses reveal (1) that many plant AAAP family proteins arose recently by multiple gene duplication events that occurred within a single organism, (2) that some plant members of the family with strikingly different specificities diverged early in evolutionary history, and (3) that AAAP family proteins from fungi and animals diverged from the plant proteins long ago, possibly when animals, plants and fungi diverged from each other. The Neurospora protein nevertheless exhibits overlapping specificity with those found in plants. Preliminary evidence is presented suggesting that proteins of the AAAP family are distantly related to proteins of the large ubiquitous amino acid/polyamine/choline family (TC #2.3) as well as to those of two small bacterial amino acid transporter families, the ArAAP family (TC #2.42) and the STP family (TC #2.43).     

The "ins and outs" of enactment: A relational bridge for psychotherapy integration.

Patients' enactments--their reflexive attempts to influence interpersonal interactions in particular ways based on their psychodynamics, both with the therapist and with others outside the psychotherapy setting--provide an important avenue for advancing the complex task of integrating action-oriented techniques with in-depth exploration. This article, written from a relational psychoanalytic perspective, shows how enactments create a valuable bridge for thinking about and practicing psychotherapy integration. To be most effective, psychotherapists must deal both behaviorally and psychodynamically with enactments, using integrative interventions that simultaneously encourage constructive new and adaptive behaviors, promote important new mutative relational experiences with therapists and with others, and facilitate deep insight. Acting together, these processes contribute to structural, including behavioral, personality reorganization. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Sex hormones and headache

A variety of evidence suggests a link between migraine and the female sex hormones. Women with migraine outnumber men by at least a 2:1 ratio and definite patterns of development and attacks are noted at menarche and throughout the period of menses, related to trimester of pregnancy, and again at menopause, although it may also regress. Hormonal replacement with estrogen can exacerbate migraine; oral contraceptives can change the character and frequency of migraine headache. This article will cover approaches to the therapy of hormone-related headaches associated with the menstrual cycle, menopause, and oral contraceptives.     

Calciotropic hormones and nephrolithiasis

In recurrent calcium stone formers interfering factors or changes in receptor sensitivity may alter the interrelationships among calcium-regulating hormones, and hormonal behavior often does not fit with the theoretical assumptions. The vitamin D system appears to have the most important metabolic and clinical effects. Abnormal up-regulation of the synthesis of calcitriol and the consequent parathyroid hormone (PTH) suppression can induce hypercalciuria. Consequently, the hypocalciuric effect of thiazide would be caused by an enhanced response to PTH and by a reduction in 1,25(OH)2-vit D. A negative role of vitamin D on the skeleton has been observed in the presence of a negative calcium balance. Moreover, vitamin D also plays a role in urine oxalate excretion. PTH seems not to be directly stimulated in hypercalciuria and recurrent calcium nephrolithiasis, and patients with hyperparathyroidism and recurrent calcium nephrolithiasis show a similar degree of bone demineralization, irrespective of the presence of absence of the so-called 'primary hyperparathyroidism.' Calcitonin plays a contributory role in the pathogenesis of recurrent calcium nephrolithiasis that seems to be strictly related to dietary calcium intake. A higher sensitivity of thyroid C cells, particularly in absorptive hypercalciuric patients, could be related to the pathogenesis of hypercalciuria and contribute to its persistence.     

Plant paralog to viral movement protein that potentiates transport of mRNA into the phloem

CmPP16 from Cucurbita maxima was cloned and the protein was shown to possess properties similar to those of viral movement proteins. CmPP16 messenger RNA (mRNA) is present in phloem tissue, whereas protein appears confined to sieve elements (SE). Microinjection and grafting studies revealed that CmPP16 moves from cell to cell, mediates the transport of sense and antisense RNA, and moves together with its mRNA into the SE of scion tissue. CmPP16 possesses the characteristics that are likely required to mediate RNA delivery into the long-distance translocation stream. Thus, RNA may move within the phloem as a component of a plant information superhighway.