Insights into the PX (phox-homology) domain and SNX (sorting nexin) protein families: structures, functions and roles in disease

2011 ◽  
Vol 441 (1) ◽  
pp. 39-59 ◽  
Author(s):  
Rohan D. Teasdale ◽  
Brett M. Collins
Keyword(s):  
Membrane Trafficking ◽  
Cell Signalling ◽  
Interaction Domain ◽  
Sorting Nexins ◽  
Pathogen Invasion ◽  
Px Domain ◽  
The Family ◽  
Endosomal Membranes ◽  
Almost All ◽  
Phox Homology

The mammalian genome encodes 49 proteins that possess a PX (phox-homology) domain, responsible for membrane attachment to organelles of the secretory and endocytic system via binding of phosphoinositide lipids. The PX domain proteins, most of which are classified as SNXs (sorting nexins), constitute an extremely diverse family of molecules that play varied roles in membrane trafficking, cell signalling, membrane remodelling and organelle motility. In the present review, we present an overview of the family, incorporating recent functional and structural insights, and propose an updated classification of the proteins into distinct subfamilies on the basis of these insights. Almost all PX domain proteins bind PtdIns3P and are recruited to early endosomal membranes. Although other specificities and localizations have been reported for a select few family members, the molecular basis for binding to other lipids is still not clear. The PX domain is also emerging as an important protein–protein interaction domain, binding endocytic and exocytic machinery, transmembrane proteins and many other molecules. A comprehensive survey of the molecular interactions governed by PX proteins highlights the functional diversity of the family as trafficking cargo adaptors and membrane-associated scaffolds regulating cell signalling. Finally, we examine the mounting evidence linking PX proteins to different disorders, in particular focusing on their emerging importance in both pathogen invasion and amyloid production in Alzheimer's disease.

scholarly journals SNX-PXA-RGS-PXC Subfamily of SNXs in the Regulation of Receptor-Mediated Signaling and Membrane Trafficking

2021 ◽  
Vol 22 (5) ◽  
pp. 2319
Author(s):  
Bibhas Amatya ◽  
Hewang Lee ◽  
Laureano D. Asico ◽  
Prasad Konkalmatt ◽  
Ines Armando ◽  
...  
Keyword(s):  
G Protein ◽  
Membrane Trafficking ◽  
Endosomal Trafficking ◽  
Receptor Signaling ◽  
Α Subunit ◽  
Sorting Nexins ◽  
Px Domain ◽  
Endosomal Membranes ◽  
Rgs Domain ◽  
The Difference

The SNX-PXA-RGS-PXC subfamily of sorting nexins (SNXs) belongs to the superfamily of SNX proteins. SNXs are characterized by the presence of a common phox-homology (PX) domain, along with other functional domains that play versatile roles in cellular signaling and membrane trafficking. In addition to the PX domain, the SNX-PXA-RGS-PXC subfamily, except for SNX19, contains a unique RGS (regulators of G protein signaling) domain that serves as GTPase activating proteins (GAPs), which accelerates GTP hydrolysis on the G protein α subunit, resulting in termination of G protein-coupled receptor (GPCR) signaling. Moreover, the PX domain selectively interacts with phosphatidylinositol-3-phosphate and other phosphoinositides found in endosomal membranes, while also associating with various intracellular proteins. Although SNX19 lacks an RGS domain, all members of the SNX-PXA-RGS-PXC subfamily serve as dual regulators of receptor cargo signaling and endosomal trafficking. This review discusses the known and proposed functions of the SNX-PXA-RGS-PXC subfamily and how it participates in receptor signaling (both GPCR and non-GPCR) and endosomal-based membrane trafficking. Furthermore, we discuss the difference of this subfamily of SNXs from other subfamilies, such as SNX-BAR nexins (Bin-Amphiphysin-Rvs) that are associated with retromer or other retrieval complexes for the regulation of receptor signaling and membrane trafficking. Emerging evidence has shown that the dysregulation and malfunction of this subfamily of sorting nexins lead to various pathophysiological processes and disorders, including hypertension.

scholarly journals The PX domain: a new phosphoinositide-binding module

2002 ◽  
Vol 115 (6) ◽  
pp. 1099-1105 ◽  
Author(s):  
Chris D. Ellson ◽  
Simon Andrews ◽  
Len R. Stephens ◽  
Phill T. Hawkins
Keyword(s):  
Cell Survival ◽  
Membrane Trafficking ◽  
Critical Role ◽  
Binding Specificity ◽  
Structural Studies ◽  
Sorting Nexins ◽  
Px Domain ◽  
Key Residues

The PX domain, which until recently was an orphan domain, has emerged as the latest member of the phosphoinositide-binding module superfamily. Structural studies have revealed that it has a novel fold and identified key residues that interact with the bound phosphoinositide, enabling some prediction of phosphoinositide-binding specificity. Specificity for PtdIns(3)P appears to be the most common, and several proteins containing PX domains localise to PtdIns(3)P-rich endosomal and vacuolar structures through their PX domains: these include the yeast t-SNARE Vam7p, mammalian sorting nexins (involved in membrane trafficking events) and the Ser/Thr kinase CISK, which is implicated in cell survival. Additionally,phosphoinositide binding to the PX domains of p40phox and p47phox appears to play a critical role in the active assembly of the neutrophil oxidase complex.

scholarly journals Vps501, a novel vacuolar SNX-BAR protein cooperates with the SEA complex to induce autophagy

2021 ◽  
Author(s):  
Shreya Goyal ◽  
Verónica A Segarra ◽  
Aaron M Stecher ◽  
Nitika ◽  
Andrew W Truman ◽  
...  
Keyword(s):  
Membrane Trafficking ◽  
Phylogenetic Analyses ◽  
Vacuolar Membrane ◽  
Membrane Remodeling ◽  
Sorting Nexins ◽  
Autophagy Induction ◽  
Severe Deficiency ◽  
Organelle Motility ◽  
Phox Homology ◽  
Vacuolar Trafficking

The sorting nexins (SNX), constitute a diverse family of molecules that play varied roles in membrane trafficking, cell signaling, membrane remodeling, organelle motility and autophagy. In particular, the SNX-BAR proteins, a SNX subfamily characterized by a C-terminal dimeric Bin/Amphiphysin/Rvs (BAR) lipid curvature domain and a conserved Phox-homology domain, are of great interest. In budding yeast, many SNX-BARs proteins have well-characterized endo-vacuolar trafficking roles. Phylogenetic analyses allowed us to identify an additional SNX-BAR protein, Vps501, with a novel endo-vacuolar role. We report that Vps501 uniquely localizes to the vacuolar membrane and works with the SEA complex to regulate autophagy. Furthermore, we found cells displayed a severe deficiency in starvation-induced/nonselective autophagy only when SEA complex subunits are ablated in combination with Vps501, indicating a cooperative role with the SEA complex during autophagy. Additionally, we found the SEA complex becomes destabilized in vps501Δsea1Δ cells, which resulted in aberrant TORC1 hyperactivity and misregulation of autophagy induction.

scholarly journals Regulation of cytokine-independent survival kinase (CISK) by the Phox homology domain and phosphoinositides

2001 ◽  
Vol 154 (4) ◽  
pp. 699-706 ◽  
Author(s):  
Jun Xu ◽  
Dan Liu ◽  
Gordon Gill ◽  
Zhou Songyang
Keyword(s):  
Membrane Trafficking ◽  
Direct Interaction ◽  
Lipid Binding ◽  
Ph Domain ◽  
Growth And Survival ◽  
Binding Domains ◽  
Px Domain ◽  
And Function ◽  
Phox Homology

PKB/Akt and serum and glucocorticoid–regulated kinase (SGK) family kinases are important downstream targets of phosphatidylinositol 3 (PI-3) kinase and have been shown to mediate a variety of cellular processes, including cell growth and survival. Although regulation of Akt can be achieved through several mechanisms, including its phosphoinositide-binding Pleckstrin homology (PH) domain, how SGK kinases are targeted and regulated remains to be elucidated. Unlike Akt, cytokine-independent survival kinase (CISK)/SGK3 contains a Phox homology (PX) domain. PX domains have been implicated in several cellular events involving membrane trafficking. However, their precise function remains unknown. We demonstrate here that the PX domain of CISK interacts with phosphatidylinositol (PtdIns)(3,5)P2, PtdIns(3,4,5)P3, and to a lesser extent PtdIns(4,5)P2. The CISK PX domain is required for targeting CISK to the endosomal compartment. Mutation in the PX domain that abolished its phospholipid binding ability not only disrupted CISK localization, but also resulted in a decrease in CISK activity in vivo. These results suggest that the PX domain regulates CISK localization and function through its direct interaction with phosphoinositides. Therefore, CISK and Akt have evolved to utilize different lipid binding domains to accomplish a similar mechanism of activation in response to PI-3 kinase signaling.

scholarly journals Structure of Sorting Nexin 11 (SNX11) Reveals a Novel Extended Phox Homology (PX) Domain Critical for Inhibition of SNX10-induced Vacuolation

2013 ◽  
Vol 288 (23) ◽  
pp. 16598-16605 ◽  
Author(s):  
Jinxin Xu ◽  
Tingting Xu ◽  
Bin Wu ◽  
Yinghua Ye ◽  
Xiaojuan You ◽  
...  
Keyword(s):  
Crystal Structures ◽  
Endosomal Trafficking ◽  
Sorting Nexins ◽  
Sorting Nexin ◽  
Px Domain ◽  
C Terminus ◽  
Phox Homology ◽  
Β Sheet

Sorting nexins are phox homology (PX) domain-containing proteins involved in diverse intracellular endosomal trafficking pathways. The PX domain binds to certain phosphatidylinositols and is recruited to vesicles rich in these lipids. The structure of the PX domain is highly conserved, containing a three-stranded β-sheet, followed by three α-helices. Here, we report the crystal structures of truncated human SNX11 (sorting nexin 11). The structures reveal that SNX11 contains a novel PX domain, hereby named the extended PX (PXe) domain, with two additional α-helices at the C terminus. We demonstrate that these α-helices are indispensible for the in vitro functions of SNX11. We propose that this PXe domain is present in SNX10 and is responsible for the vacuolation activity of SNX10. Thus, this novel PXe domain constitutes a structurally and functionally important PX domain subfamily.

Analisis Perbandingan Manajemen Keuangan Ojek Online Dan Ojek Reguler Studi Kasus Kecamatan Duren Sawit Jakarta Timur

Liquidity ◽  
2018 ◽  
Vol 7 (1) ◽  
pp. 41-52
Author(s):  
M. Koesmawan ◽  
Darwin Erhandy ◽  
Dede Dahlan
Keyword(s):  
Financial Management ◽  
Average Income ◽  
Savings And Loans ◽  
Financial Difficulties ◽  
The Family ◽  
Family Finances ◽  
The Subject ◽  
Almost All

In order to meet the needs of living which consists of primary as well as secondary needs, human can work in either a formal or an informal job. One of the informal jobs that is became the subject of this research was to become an ojek driver. Ojek is a ranting motorcycle.  Revenue of ojek drivers, accordingly, should be well managed following the concept of financial management. This research was conducted for the driver of the online motorcycle drivers as well as the regular motorcycle drivers they are called “The Ojek”. Ojek’s location is in Kecamatan (subdistrict) Duren Sawit, East Jakarta with 70 drivers of ojeks. The online ojeks earn an average of Rp 100,000 per day, can save Rp 11,000 to 21,000 per day, while, the regular ojek has an average income per day slightly lower amounted to Rp 78,500, this kind of ojeks generally have other businesses and always record the outflow of theirs money. Both the online and regular ojeks feel a tight competition in getting passengers, but their income can help the family finances and both ojeks want a cooperative especially savings and loans, especially to overcome the urgent financial difficulties. Almost all rivers, do not dare to borrow money. They are afraid of can not refund the money as scheduled.

scholarly journals Determinants of the Endosomal Localization of Sorting Nexin 1

2005 ◽  
Vol 16 (4) ◽  
pp. 2049-2057 ◽  
Author(s):  
Qi Zhong ◽  
Martin J. Watson ◽  
Cheri S. Lazar ◽  
Andrea M. Hounslow ◽  
Jonathan P. Waltho ◽  
...  
Keyword(s):  
Binding Pocket ◽  
Early Endosome ◽  
Nmr Structure ◽  
Sorting Nexin ◽  
High Affinity ◽  
Terminal Domain ◽  
Px Domain ◽  
Phox Homology ◽  
Phosphatidylinositol 3

The sorting nexin (SNX) family of proteins is characterized by sequence-related phox homology (PX) domains. A minority of PX domains bind with high affinity to phosphatidylinositol 3-phosphate [PI(3)P], whereas the majority of PX domains exhibit low affinity that is insufficient to target them to vesicles. SNX1 is located on endosomes, but its low affinity PX domain fails to localize in vivo. The NMR structure of the PX domain of SNX1 reveals an overall fold that is similar to high-affinity PX domains. However, the phosphatidylinositol (PI) binding pocket of the SNX1 PX domain is incomplete; regions of the pocket that are well defined in high-affinity PX domains are highly mobile in SNX1. Some of this mobility is lost upon binding PI(3)P. The C-terminal domain of SNX1 is a long helical dimer that localizes to vesicles but not to the early endosome antigen-1–containing vesicles where endogenous SNX1 resides. Thus, the obligate dimerization of SNX1 that is driven by the C-terminal domain creates a high-affinity PI binding species that properly targets the holo protein to endosomes.

Two new species of the genus Syngastes (Copepoda, Harpacticoida, Tegastidae) from South Korea

Crustaceana ◽  
2016 ◽  
Vol 89 (4) ◽  
pp. 431-458 ◽  
Author(s):  
Jong Guk Kim ◽  
Jong Guk Kim ◽  
Tae Won Jung ◽  
Jong Guk Kim ◽  
Tae Won Jung ◽  
...  
Keyword(s):  
New Species ◽  
South Korea ◽  
First Record ◽  
Exopodal Segment ◽  
Key To Species ◽  
Korean Waters ◽  
The Family ◽  
Two New Species ◽  
Almost All

Herein two new species of the genusSyngastesMonard, 1924 are described from South Korea, with detailed descriptions and illustrations. Both new copepods,Syngastesmulticavussp. nov. andS. pseudofoveatussp. nov., have two inner setae on the first exopodal segment of P2 and P3.Syngastesmulticavussp. nov. most closely resemblesS. gibbosusBartsch, 1999 reported from Australia, as they both have a five-segmented antennule in the female. However,Syngastesmulticavussp. nov. has a rounded body outline instead of the gibbose outline observed inS. gibbosus.Syngastespseudofoveatussp. nov. resemblesS. foveatusBartsch, 1994 in almost all aspects. However, they differ clearly in the number of setae on the first exopodal segment of P2 and P3. We also provide a key to species of the genusSyngastesworldwide. The present study is the first record of the family Tegastidae in Korean waters.

Resolving the Lourinia armata (Claus, 1866) complex with remarks on the monophyletic status of Louriniidae, Monard 1927 (Copepoda: Harpacticoida)

Zootaxa ◽  
2021 ◽  
Vol 5051 (1) ◽  
pp. 346-386
Author(s):  
SÜPHAN KARAYTUĞ ◽  
SERDAR SAK ◽  
ALP ALPER ◽  
SERDAR SÖNMEZ
Keyword(s):  
Comparative Evaluation ◽  
Species Complex ◽  
Detailed Examination ◽  
The Other ◽  
Phylogenetic Position ◽  
Nicobar Island ◽  
Other Hand ◽  
The Family ◽  
Close Relationship ◽  
Almost All

An attempt was made to test if Lourinia armata (Claus, 1866)—as it is currently diagnosed—represents a species complex. Detailed examination and comparisons of several specimens collected from different localities suggest that L. armata indeed represents a complex of four closely related morphospecies that can be differentiated from one another by only detailed observations. One of the four species is identified as Lourinia aff. armata and the other three species are described as new to science and named as Lourinia wellsi sp. nov., L. gocmeni sp. nov., and L. aldabraensis sp. nov. Detailed review of previous species records indicates that the genus Lourinia Wilson, 1924 is distributed worldwide. Ceyloniella nicobarica Sewell, 1940, originally described from Nicobar Island and previously considered a junior subjective synonym of L. armata is reinstated as Lourinia nicobarica (Sewell, 1940) comb. nov. on the basis of the unique paddle-shaped caudal ramus seta V. It is postulated that almost all of these records are unreliable in terms of representing true Lourinia aff. armata described herein. On the other hand, the comparative evaluation of the illustrations and descriptions in the published literature indicates the presence of several new species waiting to be discovered in the genus Lourinia.                 It has been determined that, according to updated modern keys, the recent inclusion of the monotypic genus Archeolourinia Corgosinho & Schizas, 2013 in the Louriniidae is not justified since Archeolourinia shermani Corgosinho & Schizas, 2013 does not belong to this family but should be assigned to the Canthocamptidae. On the other hand, it has been argued that the exact phylogenetic position of the Louriniidae still remains problematic since none of the diagnostic characters supports the monophyly of the family within the Oligoarthra. It has also been argued that the close relationship between Louriniidae and Canthocamptidae is supported since both families share the homologous sexual dimorphism (apophysis) on P3 endopod. The most important characteristic that can possibly be used to define Louriniidae is the reduction of maxilliped.  

THE PATIENT BOY—A POPULAR LESSON, READ TO CHILDREN IN THE 1820'S

PEDIATRICS ◽  
1969 ◽  
Vol 43 (4) ◽  
pp. 526-526
Author(s):  
T. E. C.
Keyword(s):  
The Family ◽  
Almost All

The story below depicts a favorite subject of those who wrote for children in the early days of our country. The inebriated father leading his family inexorably into destitution by his intemperance is counterbalanced by a son who holds the family together. During the last century many children cried over this and similar stories. The Patient Boy There was a journeyman bricklayer in this town, a good workman, but a very drunken idle fellow; he spent at the dram shop almost all he earned, and left his wife and children to take care of themselves; to get food and clothes as they could. They might all have starved, but for the eldest son, whom his father had brought up to help him at his work; and who was so industrious and attentive, that being now at the age of thirteen or fourteen, he was able to earn pretty good wages, every penny of which that he could keep out of his father's hands, he brought to his mother. When the brute of a father came home drunk, cursing and swearing, and in such an ill humour that his mother, and the rest of the children, durst not come near him for fear of a beating, this good lad (Tom was his name) kept close to him, to pacify him, and get him quietly to bed. His mother looked upon Tom as the support of the family, and loved him dearly. It happened one day, Tom in climbing up a high ladder, with a load of mortar on his head, missed his hold, and fell down to the bottom, on a heap of bricks and rubbish.

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