SignificanceIt has remained an unresolved question whether microorganisms recovered from the most arid environments on Earth are thriving under such extreme conditions or are just dead or dying vestiges of viable cells fortuitously deposited by atmospheric processes. Based on multiple lines of evidence, we show that indigenous microbial communities are present and temporally active even in the hyperarid soils of the Atacama Desert (Chile). Following extremely rare precipitation events in the driest parts of this desert, where rainfall often occurs only once per decade, we were able to detect episodic incidences of biological activity. Our findings expand the range of hyperarid environments temporarily habitable for terrestrial life, which by extension also applies to other planetary bodies like Mars.

Recent studies suggest that central nervous system synapses can persist for weeks, months, perhaps lifetimes, yet little is known as to how synapses maintain their structural and functional characteristics for so long. As a step toward a better understanding of synaptic maintenance we examined the loss, redistribution, reincorporation, and replenishment dynamics of Synapsin I and ProSAP2/Shank3, prominent presynaptic and postsynaptic matrix molecules, respectively. Fluorescence recovery after photobleaching and photoactivation experiments revealed that both molecules are continuously lost from, redistributed among, and reincorporated into synaptic structures at time-scales of minutes to hours. Exchange rates were not affected by inhibiting protein synthesis or proteasome-mediated protein degradation, were accelerated by stimulation, and greatly exceeded rates of replenishment from somatic sources. These findings indicate that the dynamics of key synaptic matrix molecules may be dominated by local protein exchange and redistribution, whereas protein synthesis and degradation serve to maintain and regulate the sizes of local, shared pools of these proteins.

Active zones are specialized regions of the presynaptic plasma membrane designed for the efficient and repetitive release of neurotransmitter via synaptic vesicle (SV) exocytosis. Piccolo is a high molecular weight component of the active zone that is hypothesized to participate both in active zone formation and the scaffolding of key molecules involved in SV recycling. In this study, we use interference RNAs to eliminate Piccolo expression from cultured hippocampal neurons to assess its involvement in synapse formation and function. Our data show that Piccolo is not required for glutamatergic synapse formation but does influence presynaptic function by negatively regulating SV exocytosis. Mechanistically, this regulation appears to be calmodulin kinase II–dependent and mediated through the modulation of Synapsin1a dynamics. This function is not shared by the highly homologous protein Bassoon, which indicates that Piccolo has a unique role in coupling the mobilization of SVs in the reserve pool to events within the active zone.

The obese gene (ob) product, leptin, has recently been shown to be produced by adipocytes and to circulate in the plasma acting as a hormone to modulate appetite and metabolism. Intriguingly, the ob/ob mutant female mouse, which does not produce an active form of leptin due to a mutation of the ob gene, has been shown to be acyclic and sterile. This sterility can be reversed by treatment with recombinant leptin, but not by diet restriction – suggesting that leptin is required for normal reproductive function. The mechanism(s) whereby leptin modulates reproductive function are unknown; however, it is possible that leptin could directly regulate reproductive tissues. To determine whether endocrine and neuroendocrine tissues could be targets for leptin action, we examined whether these tissues express the leptin receptor mRNA by utilizing reverse-transcription polymerase chain reaction (RT-PCR) analysis in selected tissues from the male and female rat. The results revealed that the leptin receptor mRNA transcript is highly expressed in the ovary, uterus and testis, moderately expressed in the hypothalamus and anterior pituitary, with low to no expression in the adrenal. The RT-PCR results were confirmed by Northern analysis. Furthermore, immortalized GnRH (GT1-7 and NLT) neurons and ovarian granulosa cells were also demonstrated by RT-PCR analysis to express the leptin receptor, suggsting that GnRH neurons and steroid-producing cells of the ovary could be targets for leptin action. Immunohistochemical studies revealed dense immunolocalization of the leptin receptor in the choroid plexus, and interestingly, in the arcuate nucleus/median eminence of the female rat – a key sit in the control of feeding and reproduction. Finally, treatment of the ob/ob mouse with recombinant leptin (0.15 mg/kg/day × 2 weeks) was found to markedly upregulate side chain cleavage and 17α-hydroxylase mRNA levels in the ovary, demonstrating that leptin, acting either through a direct or indirect mechanism, can regulate gene expression in reproductive tissues.

SAP97 is a modular protein composed of three PDZ domains, an SH3 domain, and a guanylate kinase-like domain. It has been implicated functionally in the assembly and structural stability of synaptic junctions as well as in the trafficking, recruitment, and localization of specific ion channels and neurotransmitter receptors. The N terminus of SAP97 (S97N) has been shown to play a key role in the selection of binding partners and the localization of SAP97 at adhesion sites, as well as the clustering of ion channels in heterologous cells. Using the S97N domain as bait in a yeast two-hybrid screen, we identified the minus-end-directed actin-based motor, myosin VI, as an S97N binding partner. Moreover, in light membrane fractions prepared from rat brain, we found that myosin VI and SAP97 form a trimeric complex with the ␣-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor subunit, GluR1. These data suggest that SAP97 may serve as a molecular link between GluR1 and the actin-dependent motor protein myosin VI during the dynamic translocation of AMPA receptors to and from the postsynaptic plasma membrane.The synapse-associated protein SAP97 belongs to the SAP90/ PSD-95 subfamily of membrane-associated guanylate kinase homologs (MAGUKs).

Neuronal morphogenesis, synaptogenesis and synaptic plasticity are fundamental aspects of nervous system development. Much of our current understanding of how each of these processes contributes to the establishment and maintenance of neural circuitry has come from a molecular description of specific classes of key molecules. With regard to synapse assembly and function, a family of membrane-associated guanylate kinase homologs (MAGUKs) have emerged as central organizers of multicomponent protein signaling complexes. In particular MAGUKs appear to play fundamental roles in the transport, anchoring and signaling of specific subclasses of synaptic receptors and ion channels. In this review, we will focus on the role that subfamilies of MAGUKs play during the formation, maintenance and plasticity of the vertebrate central nervous system glutamatergic synapse.

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The majority of excitatory synapses in the mammalian brain form on filopodia and spines, actin-rich membrane protrusions present on neuronal dendrites. The biochemical events that induce filopodia and remodel these structures into dendritic spines remain poorly understood. Here, we show that the neuronal actin- and protein phosphatase-1-binding protein, neurabin-I, promotes filopodia in neurons and nonneuronal cells. Neurabin-I actin-binding domain bundled F-actin, promoted filopodia, and delayed the maturation of dendritic spines in cultured hippocampal neurons. In contrast, dimerization of neurabin-I via C-terminal coiled-coil domains and association of protein phosphatase-1 (PP1) with neurabin-I through a canonical KIXF motif inhibited filopodia. Furthermore, the expression of a neurabin-I polypeptide unable to bind PP1 delayed the maturation of neuronal filopodia into spines, reduced the synaptic targeting of AMPA-type glutamate (GluR1) receptors, and decreased AMPA receptor-mediated synaptic transmission. Reduction of endogenous neurabin levels by interference RNA (RNAi)-mediated knockdown also inhibited the surface expression of GluR1 receptors. Together, our studies suggested that disrupting the functions of a cytoskeletal neurabin/PP1 complex enhanced filopodia and impaired surface GluR1 expression in hippocampal neurons, thereby hindering the morphological and functional maturation of dendritic spines.