Syntrophins entangled in cytoskeletal meshwork: Helping to hold it all together

Syntrophins are a family of 59 kDa peripheral membrane‐associated adapter proteins, containing multiple protein‐protein and protein‐lipid interaction domains. The syntrophin family consists of five isoforms that exhibit specific tissue distribution, distinct sub‐cellular localization and unique expression patterns implying their diverse functional roles. These syntrophin isoforms form multiple functional protein complexes and ensure proper localization of signalling proteins and their binding partners to specific membrane domains and provide appropriate spatiotemporal regulation of signalling pathways. Syntrophins consist of two PH domains, a PDZ domain and a conserved SU domain. The PH1 domain is split by the PDZ domain. The PH2 and the SU domain are involved in the interaction between syntrophin and the dystrophin‐glycoprotein complex (DGC). Syntrophins recruit various signalling proteins to DGC and link extracellular matrix to internal signalling apparatus via DGC. The different domains of the syntrophin isoforms are responsible for modulation of cytoskeleton. Syntrophins associate with cytoskeletal proteins and lead to various cellular responses by modulating the cytoskeleton. Syntrophins are involved in many physiological processes which involve cytoskeletal reorganization like insulin secretion, blood pressure regulation, myogenesis, cell migration, formation and retraction of focal adhesions. Syntrophins have been implicated in various pathologies like Alzheimer’s disease, muscular dystrophy, cancer. Their role in cytoskeletal organization and modulation makes them perfect candidates for further studies in various cancers and other ailments that involve cytoskeletal modulation. The role of syntrophins in cytoskeletal organization and modulation has not yet been comprehensively reviewed till now. This review focuses on syntrophins and highlights their role in cytoskeletal organization, modulation and dynamics via its involvement in different cell signalling networks.     

Mycobacterial biofilms: a greasy way to hold it together

Microorganisms growing on surfaces can form biofilms under certain conditions. In this issue of Cell, Ojha et al. (2005) investigate biofilm formation in mycobacteria. They identify new cell-wall components that are required for the formation of architecturally complex mature biofilms in these bacteria and the surprising involvement of a chaperone protein in this process.     

Clathrin-associated adaptor proteins - putting it all together

Adaptors are multifunctional linker proteins that, as a coated vesicle assembles, tether the clathrin lattice to the underlying membrane bud site. Each adaptor is composed of four distinct protein submits, but how these assemble into the functional complex is not clear. Here, some features of the protein sequences are discussed in an attempt to develop a speculative, low-resolution structural model of possible subunit interactions.     

Putting it all together: intrinsic and extrinsic mechanisms governing proteasome biogenesis

Background

The 26S proteasome is at the heart of the ubiquitin-proteasome system, which is the key cellular pathway for the regulated degradation of proteins and enforcement of protein quality control. The 26S proteasome is an unusually large and complicated protease comprising a 28-subunit core particle (CP) capped by one or two 19-subunit regulatory particles (RP). Multiple activities within the RP process incoming ubiquitinated substrates for eventual degradation by the barrel-shaped CP. The large size and elaborate architecture of the proteasome have made it an exceptional model for understanding mechanistic themes in macromolecular assembly.

Objective

In the present work, we highlight the most recent mechanistic insights into proteasome assembly, with particular emphasis on intrinsic and extrinsic factors regulating proteasome biogenesis. We also describe new and exciting questions arising about how proteasome assembly is regulated and deregulated in normal and diseased cells.

Methods

A comprehensive literature search using the PubMed search engine was performed, and key findings yielding mechanistic insight into proteasome assembly were included in this review.

Results

Key recent studies have revealed that proteasome biogenesis is dependent upon intrinsic features of the subunits themselves as well as extrinsic factors, many of which function as dedicated chaperones.

Conclusion

Cells rely on a diverse set of mechanistic strategies to ensure the rapid, efficient, and faithful assembly of proteasomes from their cognate subunits. Importantly, physiological as well as pathological changes to proteasome assembly are emerging as exciting paradigms to alter protein degradation in vivo.

     

Integrins hold Drosophila together

The Drosophila position-specific (PS) integrins are members of the integrin family of cell surface receptors and are thought to be receptors for extracellular matrix components. Each PS integrin consists of an α subunit, α_PS1 or α_PS2, and a β_PS subunit. Mutations in the β_PS subunit and the α_PS2 subunit have been characterised and reveal that the PS integrins have an essential role in the adhesion of different cell layers to each other. The PS integrins are especially required for the function of the cell-matrix-cell junctions, where the muscles attach to the epidermis and where one surface of the developing wing adheres to the other. These junctions are similar to vertebrate focal adhesions and hemidesmosomes, which also contain integrins. Integrin-mediated cell to cell adhesion via the extracellular matrix provides a way for tissues to adhere to each other without intermingling of their cells.     

Flagellar motility: all pull together

Eukaryotic flagella produce a swimming force by coordinating thousands of dynein motor proteins. Recent work provides new clues into how this coordination is achieved.     

DNA repair: keeping it together

A protein scaffold has been identified that holds a chromosome together in the event of a DNA double-strand break. This scaffold is dependent on Rad52 and the Rad50-Mre11-Xrs2 complex and withstands the pulling forces of the mitotic spindle during DNA damage checkpoint arrest.     

Color vision: putting it together

Color vision depends on the visual system comparing signals that originate in different classes of cone photoreceptors. New work shows that the different classes of cones are not only distributed irregularly, but in different individuals they are present in very variable proportions. Surprisingly, this does not affect color vision.     

Holding it together: chromatin in the Archaea

Recently, several advances have been made in the understanding of the form and function of archaeal chromatin. Remarkable parallels can be drawn between the structure and modification of chromatin components in the archaeal and the eukaryotic domains of life. Indeed, it now appears that key components of the hugely complex eukaryotic chromatin regulatory machinery were established before the divergence of the archaeal and eukaryotic lineages.     

Electrostatic fasteners hold the T cell receptor-CD3 complex together

Assembly of the T cell receptor includes the formation of trimers stabilized by electrostatic interactions inside the membrane (Call et al., 2003). Such interactions can strongly stabilize subunit associations while permitting conformation changes during signaling.