Posts Tagged ‘conserved’

The conservation of space-time.

In physics, the conservation laws state the measurable property of an isolated physical system does not change as the system evolves over time. They include the laws of conservation of energy, linear momentum, angular momentum, and electric charge. Einstein’s General Relativity, from 1905 to 2005 – Kip Thorne – However these laws suggest the existence […]

Dopaminergic inhibition of gonadotropin-releasing hormone neurons in the cichlid fish, Astatotilapia burtoni [SHORT COMMUNICATION]

Astra S. Bryant, Anna K. Greenwood, Scott A. Juntti, Allie E. Byrne, and Russell D. FernaldDopamine regulates reproduction in part by modulating neuronal activity within the hypothalamic-pituitary-gonadal (HPG) axis. Previous studies suggested numerou…

A cross-modal genetic framework for the development and plasticity of sensory pathways

Modality-specific sensory inputs from individual sense organs are processed in parallel in distinct areas of the neocortex. For each sensory modality, input follows a cortico–thalamo–cortical loop in which a ‘first-order’ exteroceptive thalamic nucleus sends peripheral input to the primary sensory cortex, which projects back to a ‘higher order’ thalamic nucleus that targets a secondary sensory cortex. This conserved circuit motif raises the possibility that shared genetic programs exist across sensory modalities. Here we report that, despite their association with distinct sensory modalities, first-order nuclei in mice are genetically homologous across somatosensory, visual, and auditory pathways, as are higher order nuclei. We further reveal peripheral input-dependent control over the transcriptional identity and connectivity of first-order nuclei by showing that input ablation leads to induction of higher-order-type transcriptional programs and rewiring of higher-order-directed descending cortical input to deprived first-order nuclei. These findings uncover an input-dependent genetic logic for the design and plasticity of sensory pathways, in which conserved developmental programs lead to conserved circuit motifs across sensory modalities.

Atomic structure of the entire mammalian mitochondrial complex I

Mitochondrial complex I plays a key role in cellular energy production by transferring electrons from NADH to ubiquinone coupled to proton translocation across the membrane1,2. It is the largest protein assembly of the respiratory chain with total mass of 970 kDa3. Here we present a nearly complete atomic structure of ovine mitochondrial complex I at 3.9 Å resolution, solved by cryo-electron microscopy aided by crosslinking/mass-spectrometry mapping. All 14 conserved core and 31 mitochondria-specific supernumerary subunits are resolved within the L-shaped molecule. The hydrophilic matrix arm harbours FMN and 8 iron-sulphur clusters involved in electron transfer, and the membrane arm contains 78 transmembrane helices, mostly contributed by antiporter-like subunits involved in proton translocation. Supernumerary subunits form an interlinked, stabilizing shell around the conserved core. Tightly bound lipids (including cardiolipins) further stabilize interactions between the hydrophobic subunits. Subunits with possible regulatory roles contain additional cofactors, NADPH and two phosphopantetheine molecules, revealed to be involved in inter-subunit interactions. We observe two different conformations of the complex, which may be related to the conformationally driven coupling mechanism and to the active/deactive transition of the enzyme. Our structure provides insight into complex I mechanism, assembly, maturation and dysfunction, allowing detailed molecular analysis of disease-causing mutations.

An evolutionarily conserved pathway controls proteasome homeostasis

The proteasome is essential for the selective degradation of most cellular proteins, but how cells maintain adequate amounts of proteasome is unclear. Here we show that there is an evolutionarily conserved signalling pathway controlling proteasome homeostasis. Central to this pathway is TORC1, the inhibition of which induced all known yeast 19S regulatory particle assembly-chaperones (RACs), as well as proteasome subunits. Downstream of TORC1 inhibition, the yeast mitogen-activated protein kinase, Mpk1, acts to increase the supply of RACs and proteasome subunits under challenging conditions in order to maintain proteasomal degradation and cell viability. This adaptive pathway was evolutionarily conserved, with mTOR and ERK5 controlling the levels of the four mammalian RACs and proteasome abundance. Thus, the central growth and stress controllers, TORC1 and Mpk1/ERK5, endow cells with a rapid and vital adaptive response to adjust proteasome abundance in response to the rising needs of cells. Enhancing this pathway may be a useful therapeutic approach for diseases resulting from impaired proteasomal degradation.

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