BioEssays in phosphoinositides: A special collection

We are pleased to introduce to our readers a special collection of BioEssays on phosphoinositides (PtdInsPs), which can be found at: http://onlinelibrary.wiley.com/journal/10.1002/%28ISSN%291521-1878/homepage/phosphoinositides_special_collection.htm. PtdInsPs are versatile phospholipid second messengers that play an important role in many aspects of cell function including cell proliferation, signal transduction, organelle biogenesis and identity, membrane trafficking, and even nuclear dynamics. This diverse functional portfolio arises in part because (i) each PtdInsP has a specialized sub-cellular localization, (ii) each PtdInsP species regulates its own set of protein effectors, which can number in the dozens, (iii) PtdInsPs can be interconverted by a series of lipid kinases and phosphatases, and (iv) PtdInsP signaling is integrated and cross-talks with other molecular modulators such as members of the Rab family of small GTPases. Thus, despite being “simple” lipids, understanding the regulation, function, and relationship between each PtdInsP poses a tremendous challenge. Nevertheless, given their significance in cell physiology, health, and disease, it is imperative that we address paucities in our understanding of PtdInsP function and regulation. To help achieve this, we hope that this special issue of BioEssays will be a valuable resource for specialists and non-specialists to review and learn about each PtdInsP and the numerous fundamental questions that remain unanswered. The special collection is composed of seven articles, one for each of the seven PtdInsP species. Importantly, we plan to append additional relevant articles over time. Starting with the mono-phosphorylated PtdInsP species, Schink et al. 1 evaluate our present view of the regulation and function of PtdIns(3)P, a lipid implicated in endosome dynamics, autophagy, exocytosis, and signal transduction, among other processes. The diverse roles of PtdIns(3)P are articulated by binding to a plethora of effectors, many of which contain a FYVE or a PX domain. Schink et al. also stress some of the important tools available to investigate PtdIns(3)P. In comparison, De Matteis et al. 2 focus on the biology of PtdIns(4)P, a lipid most associated with Golgi function and secretion. Nevertheless, its functional repertoire now includes roles in endocytic trafficking, endoplasmic reticulum export, and plasma membrane-associated functions. Indeed, plasma membrane-localized PtdIns(4)P may have been relegated for far too long to “just being a precursor for PtdIns(4,5)P2” – a perception that may be in its last throes. Moreover, Viaud et al. 3 champion the emerging roles of PtdIns(5)P, easily the least understood of the seven PtdInsPs. Recent progress shows that PtdIns(5)P may be a key protagonist in host-pathogen interactions, vesicular trafficking, and cytoskeletal dynamics. Perhaps unexpectedly for a lipid, PtdIns(5)P may be best understood in the context of nuclear dynamics, chromatin remodeling, and gene expression. The next three articles focus on the three bis-phosphorylated species. McCartney et al. 4 provide an in-depth look at PtdIns(3,5)P2, on which there has been a surge of interest since the discovery that defects in its regulatory machinery are linked to neurodegenerative ailments. Initially discovered as a modulator of the late endosome/lysosome size, its functions now include autophagosome resolution, ion transport, and modulation of gene expression. Interestingly, PtdIns(3,5)P2 levels are controlled by a protein complex that couples an antagonistic lipid kinase and phosphatase – understanding how these enzymes are coordinated presents a fascinating challenge. In Sun et al. 5, PtdIns(4,5)P2 takes center stage. While PtdIns(4,5)P2 was discovered as a source of other second messengers, it is now known to directly modulate hundreds of protein effectors. Sun et al. review recent discoveries on how PtdIns(4,5)P2 is synthesized and consumed, and elaborate on a question that has been asked many times: where in the cell is PtdIns(4,5)P2? These authors then expound on how PtdIns(4,5)P2 influences epithelial cell polarity, morphology, and differentiation, among other processes. In the end, one cannot but wonder how a small molecule that has been studied for decades still holds so many secrets. Xie et al. 6 elaborate on the biology of PtdIns(3,4)P2, a PtdInsP with its own specific effectors, but which is often obscured by its tris-phosphorylated sibling, PtdIns(3,4,5)P3. As with other PtdInsPs, there are many routes to make and consume PtdIns(3,4)P2. Often we focus on the lipid kinase routes, but as discussed in Xie et al., phosphatases are often as important – thus, the authors focus on the role of the PtdIns(3,4,5)P3 5-phosphatases, SHIP1 and SHIP2, as majors sources of PtdIns(3,4)P2. They expand on the functional role of this lipid and of the SHIP phosphatases in regulating cytoskeletal dynamics and receptor tyrosine kinase signaling. The article ends by speculating on the possible independent roles of SHIP as a phosphatase versus as a scaffolding protein. The final article in this series is by Salamon and Backer 7 and it reviews PtdIns(3,4,5)P3. As with PtdIns(4,5)P2, PtdIns(3,4,5)P3 is incredibly well studied because of its role in cell proliferation and growth, which underpin tumorgenesis and cancer. While the authors discuss the general importance of PtdIns(3,4,5)P3, their focal point is on the regulation and function of the various class I PtdIns 3-kinases that are responsible for a significant portion of PtdIns(3,4,5)P3 synthesis. In particular, Salamon and Backer illuminate how differential regulation of class I PtdIns 3-kinase isoforms can lead to the production of distinct pools of PtdIns(3,4,5)P3 that elicit differential functions. Overall, this special collection of BioEssays on PtdInsPs brings under one umbrella a significant body of knowledge on PtdInsPs, highlighting key challenges and knowledge gaps. Combined, these articles reveal the biological richness encompassed by these small regulatory phospholipids, and the multifaceted nature of PtdInsP regulation. This complexity is underscored by the ability of PtdInsPs to interconvert, which generates ambiguity in our interpretation of which PtdInsP does what. Thus, despite decades of investigation, it appears that we are still merely scratching the surface of how and what these lipids do … Roberto J. Botelho [email protected] Department of Chemistry and Biology, Ryerson University, Toronto, ON, Canada Roberto J. Botelho Guest Editor and BioEssays Editorial Board Member

Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.