The signal recognition particle (SRP) and its receptor comprise a universally conserved and essential cellular machinery that couples the synthesis of nascent proteins to their proper membrane localization. The past decade has witnessed an explosion in in-depth mechanistic investigations of this targeting machine at increasingly higher resolution. In this review, we summarize recent work that elucidates how the SRP and SRP receptor interact with the cargo protein and the target membrane, respectively, and how these interactions are coupled to a novel GTPase cycle in the SRP•SRP receptor complex to provide the driving force and enhance the fidelity of this fundamental cellular pathway. We also discuss emerging frontiers where important questions remain to be addressed.

Ubiquitylation is an essential posttranslational modification that controls cell division, differentiation, and survival in all eukaryotes. By combining multiple E3 ligases (writers), ubiquitin-binding effectors (readers), and de-ubiquitylases (erasers) with functionally distinct ubiquitylation tags, the ubiquitin system constitutes a powerful signaling network that is employed in similar ways from yeast to humans. Here, we discuss conserved principles of ubiquitin-dependent signaling that illustrate how this posttranslational modification shapes intracellular signaling networks to establish robust development and homeostasis throughout the eukaryotic kingdom.

Abstract-Wireless Local Area Network (WLAN) has become a promising choice for indoor positioning as the only existing and established infrastructure, to localize the mobile and stationary users indoors. However, since WLAN has been initially designed for wireless networking and not positioning, the localization task based on WLAN signals has several challenges. Amongst the WLAN positioning methods, WLAN fingerprinting localization has recently achieved great attention due to its promising results. WLAN fingerprinting faces several challenges and hence, in this paper, our goal is to overview these challenges and the state-of-the-art solutions. This paper consists of three main parts: 1) Conventional localization schemes; 2) State-of-the-art approaches; 3) Practical deployment challenges. Since all the proposed methods in WLAN literature have been conducted and tested in different settings, the reported results are not equally comparable. So, we compare some of the main localization schemes in a single real environment and assess their localization accuracy, positioning error statistics, and complexity. Our results depict illustrative evaluation of WLAN localization systems and guide to future improvement opportunities.

The ubiquitin ligase CUL3 is an essential regulator of neural crest specification whose aberrant activation has been linked to autism, schizophrenia, and hypertension. CUL3 exerts its roles by pairing with ∼90 distinct substrate adaptors, yet how the different CUL3-complexes are activated is poorly understood. Here, we show that CUL3 and its adaptor KLHL12 require two calcium-binding proteins, PEF1 and ALG2, for recognition of their substrate SEC31. PEF1 and ALG2 form a target-specific co-adaptor that translates a transient rise in cytosolic calcium levels into more persistent SEC31 ubiquitylation, which in turn triggers formation of large COPII coats and promotes collagen secretion. As calcium also instructs chondrocyte differentiation and collagen synthesis, calcium-dependent control of CUL3 integrates collagen secretion into broader programs of craniofacial bone formation. Our work, therefore, identifies both calcium and CUL3 co-adaptors as important regulators of ubiquitylation events that control human development.

No abstract

Roughly one third of the proteome is initially destined for the eukaryotic endoplasmic reticulum or the bacterial plasma membrane1. The proper localization of these proteins is mediated by a universally conserved protein targeting machinery, the signal recognition particle (SRP), which recognizes ribosomes carrying signal sequences2–4 and, via interactions with the SRP receptor5,6, delivers them to the protein translocation machinery on the target membrane7. The SRP is an ancient ribonucleoprotein particle containing an essential, elongated SRP RNA whose precise functions have remained elusive. Here, we used single molecule fluorescence microscopy to demonstrate that the SRP-receptor GTPase complex, after initial assembly at the tetraloop end of SRP RNA, travels over 100 Å to the distal end of this RNA where rapid GTP hydrolysis occurs. This movement is negatively regulated by the translating ribosome and, at a later stage, positively regulated by the SecYEG translocon, providing an attractive mechanism to ensure the productive exchange of the targeting and translocation machineries at the ribosome exit site with exquisite spatial and temporal accuracy. Our results show that large RNAs can act as molecular scaffolds that enable the facile exchange of distinct factors and precise timing of molecular events in a complex cellular process; this concept may be extended to similar phenomena in other ribonucleoprotein complexes.

A Global Positioning System (GPS) receiver uses satellite signals to determine position, velocity, and timing information. Measurements are obtained by synchronising the locally generated signal in the receiver with the signals received. A synchronisation procedure called acquisition adjusts the code phases of the incoming signal and the locally generated pseudo-random replica sequence of the corresponding satellite to a small timing offset and finds the residual frequency modulation after carrier wipe-off. New fast techniques for acquiring signals indoors in conditions that require a significant number of computations are presented. In this work many arithmetic operations are shared when exploring different search options by using fast Fourier transform (FFT) and a technique based on the frequency domain replica shifting. It is shown that FFT can be used for the joint processing of multiple (code-phase/frequency) search options in both dimensions at once. With a slight degradation in performance, the algorithm has a modified version that implements the technique using two-dimensional FFT. Several possible processing schemes are presented. Moreover, the presented shifting replica approach in the frequency domain can significantly reduce computational complexity by jointly acquiring different satellites.

Phospholipid binding leads to accelerated assembly of the bacterial SRP receptor FtsY and SRP, allowing cargo proteins to be delivered to target membranes more efficiently.