Auxiliary Subunit GSG1L Acts to Suppress Calcium-Permeable AMPA Receptor Function

UNLABELLED: AMPA-type glutamate receptors are ligand-gated cation channels responsible for a majority of the fast excitatory synaptic transmission in the brain. Their behavior and calcium permeability depends critically on their subunit composition and the identity of associated auxiliary proteins. Calcium-permeable AMPA receptors (CP-AMPARs) contribute to various forms of synaptic plasticity, and their dysfunction underlies a number of serious neurological conditions. For CP-AMPARs, the prototypical transmembrane AMPAR regulatory protein stargazin, which acts as an auxiliary subunit, enhances receptor function by increasing single-channel conductance, slowing channel gating, increasing calcium permeability, and relieving the voltage-dependent block by endogenous intracellular polyamines. We find that, in contrast, GSG1L, a transmembrane auxiliary protein identified recently as being part of the AMPAR proteome, acts to reduce the weighted mean single-channel conductance and calcium permeability of recombinant CP-AMPARs, while increasing polyamine-dependent rectification. To examine the effects of GSG1L on native AMPARs, we manipulated its expression in cerebellar and hippocampal neurons. Transfection of GSG1L into mouse cultured cerebellar stellate cells that lack this protein increased the inward rectification of mEPSCs. Conversely, shRNA-mediated knockdown of endogenous GSG1L in rat cultured hippocampal pyramidal neurons led to an increase in mEPSC amplitude and in the underlying weighted mean single-channel conductance, revealing that GSG1L acts to suppress current flow through native CP-AMPARs. Thus, our data suggest that GSG1L extends the functional repertoire of AMPAR auxiliary subunits, which can act not only to enhance but also diminish current flow through their associated AMPARs. SIGNIFICANCE STATEMENT: Calcium-permeable AMPA receptors (CP-AMPARs) are an important group of receptors for the neurotransmitter glutamate. These receptors contribute to various forms of synaptic plasticity, and alterations in their expression or regulation are also seen in a number of serious neurological conditions, including stroke, motor neuron disease, and cocaine addiction. Several groups of auxiliary transmembrane proteins have been described that enhance the function and cell-surface expression of AMPARs. We now report that the recently identified auxiliary protein GSG1L decreases weighted mean channel conductance and calcium permeability of CP-AMPARs while increasing polyamine-dependent rectification by diminishing outward current. Our experiments reveal that GSG1L is an auxiliary subunit that can markedly suppress CP-AMPAR function, in both recombinant systems and central neurons

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Analisis Metode Pelaksanaan Plat Precast Dengan Plat Konvensional Ditinjau Dari Waktu Dan Biaya (Studi Kasus : Markas Komando Daerah Militer Manado)

Pemilihan metode pelaksanaan suatu proyek konstruksi sangat penting karena metode pelaksanaan yang tepat dapat memberikan hasil yang maksimal terutama jika ditinjau dari segi biaya maupun waktu. Salah satu USAha yang dilakukan oleh pengelola proyek adalah mengganti cara –cara konvensional menjadi lebih modern, yaitu dengan cara penerapan beton pracetak. Tujuan penelitian ini : (1) membandingkan metode pelaksanaan pembangunan antara penggunaan sistem beton konvensional. (2) Menganalisa biaya yang diperlukan pada kedua sistem tersebut dengan perhitungan Rab. (3) Menganalisa pengaruh waktu pelaksanaan antara sistem konvensional dan Precast terhadap biaya dengan Kurva S dari kedua sistem tersebut. Dari hal-hal tersebut akan diketahui sistem pengecoran mana yang efisien dari segi waktu, biaya, peralatan, maupun faktor pendukung, serta membandingkan antara precast fabrikasi dengan precast cast in situ. Beberapa aspek tentunya berbeda, baik untuk waktu, alat maupun proses yang akan dilakukan. Hasil penelitian memperlihatkan bahwa : dengan menggunakan metode precast membutuhkan waktu pelaksanaan selama 198 hari dengan Total biaya langsungnya adalah Rp 30,352,740,000,00, sedang untuk metode konvensional membutuhkan waktu pelaksanaan selama 226 hari dengan total biaya langsung Rp 30,230,145,000,00. Perbandingan biaya adalah Rp 122,595,000,00 sedang perbandingan waktu adalah 28 hari. Dapat disimpulkan bahwa pekerjaan menggunakan sistem precast membutuhkan biaya yang lebih besar dibandingkan sistem konvensional akan tetapi dengan waktu pengerjaan yang lebih singkat. Semakin besar volume pekerjaan dengan menggunakan sistem precast, semakin murah pula harganya dibandingkan dengan metode konvensional dan waktu pelaksanaannya juga lebih cepat, apalagi dengan menggunakan sistem Precast cast in situ