scholarly journals Faculty Opinions recommendation of Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved.

2009 ◽  
Author(s):  
James Briscoe
Keyword(s):  
Protein Function ◽  
Hedgehog Signaling ◽  
Evolutionarily Conserved

scholarly journals Cilium-independent regulation of Gli protein function by Sufu in Hedgehog signaling is evolutionarily conserved

2009 ◽  
Vol 23 (16) ◽  
pp. 1910-1928 ◽  
Author(s):  
M.-H. Chen ◽  
C. W. Wilson ◽  
Y.-J. Li ◽  
K. K. L. Law ◽  
C.-S. Lu ◽  
...  
Keyword(s):  
Protein Function ◽  
Hedgehog Signaling ◽  
Evolutionarily Conserved

scholarly journals iProteinDB: an integrative database of Drosophila post-translational modifications

2018 ◽  
Author(s):  
Yanhui Hu ◽  
Richelle Sopko ◽  
Verena Chung ◽  
Romain A. Studer ◽  
Sean D. Landry ◽  
...  
Keyword(s):  
Protein Interactions ◽  
Protein Function ◽  
Large Scale ◽  
Model Organisms ◽  
General Strategy ◽  
Post Translational Modification ◽  
Post Translational Modifications ◽  
Functional Sites ◽  
Evolutionarily Conserved ◽  
And Function

AbstractPost-translational modification (PTM) serves as a regulatory mechanism for protein function, influencing stability, protein interactions, activity and localization, and is critical in many signaling pathways. The best characterized PTM is phosphorylation, whereby a phosphate is added to an acceptor residue, commonly serine, threonine and tyrosine. As proteins are often phosphorylated at multiple sites, identifying those sites that are important for function is a challenging problem. Considering that many phosphorylation sites may be non-functional, prioritizing evolutionarily conserved phosphosites provides a general strategy to identify the putative functional sites with regards to regulation and function. To facilitate the identification of conserved phosphosites, we generated a large-scale phosphoproteomics dataset from Drosophila embryos collected from six closely-related species. We built iProteinDB (https://www.flyrnai.org/tools/iproteindb/), a resource integrating these data with other high-throughput PTM datasets, including vertebrates, and manually curated information for Drosophila. At iProteinDB, scientists can view the PTM landscape for any Drosophila protein and identify predicted functional phosphosites based on a comparative analysis of data from closely-related Drosophila species. Further, iProteinDB enables comparison of PTM data from Drosophila to that of orthologous proteins from other model organisms, including human, mouse, rat, Xenopus laevis, Danio rerio, and Caenorhabditis elegans.

Insights into biological functions across species: examining the role of Rab proteins in YIP1 family function

2005 ◽  
Vol 33 (4) ◽  
pp. 614-618 ◽  
Author(s):  
C.Z. Chen ◽  
R.N. Collins
Keyword(s):  
Membrane Proteins ◽  
Protein Function ◽  
Evolutionary Conservation ◽  
Biological Role ◽  
Rab Proteins ◽  
Biological Functions ◽  
Human Homologue ◽  
Family Function ◽  
Evolutionarily Conserved

The YIP1 family comprises an evolutionarily conserved group of membrane proteins, which share the ability to bind di-prenylated Rab proteins. The biochemical capability of YIP1 family proteins suggests a possible role in the cycle of physical localization of Rab proteins between their cognate membranes and the cytosol. YIP1 is essential for viability in yeast and a deletion of YIP1 can be rescued with the human homologue YIP1A. We have made use of this evolutionary conservation of function to generate a series of mutant alleles of YIP1 to investigate the biological role of Yip1p. Our findings indicate evidence for the participation of Yip1p in both Rab and COPII protein function; at present, we are not able to distinguish between the models that these roles represent, i.e. independent or dependent activities of Yip1p.

Gli proteins encode context-dependent positive and negative functions: implications for development and disease

Development ◽  
1999 ◽  
Vol 126 (14) ◽  
pp. 3205-3216 ◽  
Author(s):  
A. Ruiz i Altaba
Keyword(s):  
Nuclear Localization ◽  
Protein Function ◽  
Hedgehog Signaling ◽  
Functional Divergence ◽  
Dominant Negative ◽  
Full Length ◽  
Gli Proteins ◽  
A Cell ◽  
Context Dependent ◽  
Modified Forms

Several lines of evidence implicate zinc finger proteins of the Gli family in the final steps of Hedgehog signaling in normal development and disease. C-terminally truncated mutant GLI3 proteins are also associated with human syndromes, but it is not clear whether these C-terminally truncated Gli proteins fulfil the same function as full-length ones. Here, structure-function analyses of Gli proteins have been performed using floor plate and neuronal induction assays in frog embryos, as well as induction of alkaline phosphatase (AP) in SHH-responsive mouse C3H10T1/2 (10T1/2) cells. These assays show that C-terminal sequences are required for positive inducing activity and cytoplasmic localization, whereas N-terminal sequences determine dominant negative function and nuclear localization. Analyses of nuclear targeted Gli1 and Gli2 proteins suggest that both activator and dominant negative proteins are modified forms. In embryos and COS cells, tagged Gli cDNAs yield C-terminally deleted forms similar to that of Ci. These results thus provide a molecular basis for the human Polydactyly type A and Pallister-Hall Syndrome phenotypes, derived from the deregulated production of C-terminally truncated GLI3 proteins. Analyses of full-length Gli function in 10T1/2 cells suggest that nuclear localization of activating forms is a regulated event and show that only Gli1 mimics SHH in inducing AP activity. Moreover, full-length Gli3 and all C-terminally truncated forms act antagonistically whereas Gli2 is inactive in this assay. In 10T1/2 cells, protein kinase A (PKA), a known inhibitor of Hh signaling, promotes Gli3 repressor formation and inhibits Gli1 function. Together, these findings suggest a context-dependent functional divergence of Gli protein function, in which a cell represses Gli3 and activates Gli1/2 prevents the formation of repressor Gli forms to respond to Shh. Interpretation of Hh signals by Gli proteins therefore appears to involve a fine balance of divergent functions within each and among different Gli proteins, the misregulation of which has profound biological consequences.

scholarly journals Hedgehog signaling regulates neurogenesis in the larval and adult zebrafish hypothalamus

2019 ◽  
Author(s):  
Ira Male ◽  
A. Tuba Ozacar ◽  
Rita R. Fagan ◽  
Matthew Loring ◽  
Meng-Chieh Shen ◽  
...  
Keyword(s):  
Cell Signaling ◽  
Hedgehog Signaling ◽  
Radial Glia ◽  
Proper Function ◽  
Adult Zebrafish ◽  
Evolutionarily Conserved ◽  
Slow Cycling ◽  
Necessary And Sufficient ◽  
First Time ◽  
Cell Cell

AbstractWhile neurogenesis in the adult hypothalamus is now known to be essential for proper function, the cell-cell signaling events that regulate neurogenesis in this evolutionarily conserved brain region remain poorly understood. Here we show that Hedgehog (Hh)/Gli signaling positively regulates hypothalamic neurogenesis in both larval and adult zebrafish and is necessary and sufficient for normal hypothalamic proliferation rates. Hedgehog-responsive cells are relatively rapidly proliferating pluripotent neural precursors that give rise to dopaminergic, serotonergic, and GABAergic neurons. in situ and transgenic reporter analyses revealed substantial heterogeneity in cell-cell signaling within the hypothalamic niche, with slow cycling Nestin-expressing cells residing among distinct and overlapping populations of Sonic Hh (Shh)-expressing, Hh-responsive, Notch-responsive, and Wnt-responsive radial glia. This work shows for the first time that Hh/Gli-signaling is a key component of the complex cell-cell signaling environment that regulates hypothalamic neurogenesis throughout life.

The roles of peptidyl-proline isomerases in gene regulation1This review is part of Special Issue entitled Asilomar Chromatin and has undergone the Journal’s usual peer review process.

2012 ◽  
Vol 90 (1) ◽  
pp. 55-69 ◽  
Author(s):  
David Dilworth ◽  
Geoff Gudavicius ◽  
Andrew Leung ◽  
Christopher J. Nelson
Keyword(s):  
Protein Function ◽  
Peer Review Process ◽  
Post Translational Modification ◽  
Multiple Control ◽  
Proline Isomerization ◽  
Evolutionarily Conserved ◽  
Covalent Modifications ◽  
And Function ◽  
Fk506 Binding Proteins ◽  
Substrate Proteins

The post-translational modification of proteins and enzymes provides a dynamic and reversible means to control protein function and transmit biological signals. While covalent modifications such as phosphorylation and acetylation have drawn much attention, in the past decade the involvement of peptidyl-proline isomerases (PPIs) in signaling and post-translational modification of protein function has become increasingly apparent. Three distinct families of PPI enzymes (parvulins, cyclophilins, and FK506-binding proteins (FKBPs)) each have the capacity to catalyze cis–trans proline isomerization in substrate proteins, and this modification can regulate both structure and function. In eukaryotic cells, a subset of these enzymes is localized to the nucleus, where they regulate gene expression at multiple control points. Here we summarize this body of work that together establishes a clear role of these enzymes as evolutionarily conserved players in the control of both transcription of mRNAs and the assembly of chromatin.

scholarly journals Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state

2021 ◽  
pp. mbc.E20-09-0584
Author(s):  
Sapan Borah ◽  
David J. Thaller ◽  
Zhanna Hakhverdyan ◽  
Elisa C. Rodriguez ◽  
Anthony W. Isenhour ◽  
...  
Keyword(s):  
Protein Function ◽  
Structural Integrity ◽  
Integral Membrane Proteins ◽  
Interaction Networks ◽  
Nuclear Pore ◽  
Control Mechanisms ◽  
Winged Helix ◽  
Biochemical Interaction ◽  
Evolutionarily Conserved ◽  
Ring Complex

Integral membrane proteins of the Lap2-emerin-MAN1 (LEM) family have emerged as important components of the inner nuclear membrane (INM) required for the functional and physical integrity of the nuclear envelope. However, like many INM proteins, there is limited understanding of the biochemical interaction networks that enable LEM protein function. Here, we show that Heh2/Man1 can interact with major scaffold components of the nuclear pore complex (NPC), specifically the inner ring complex (IRC), in evolutionarily distant yeasts. Although an N-terminal domain is required for Heh2 targeting to the INM, we demonstrate that stable interactions with the NPC are mediated by a C-terminal winged helix (WH) domain, thus decoupling INM targeting and NPC binding. Inhibiting Heh2’s interactions with the NPC by deletion of the Heh2 WH domain leads to NPC clustering. Interestingly, Heh2’s association with NPCs can also be disrupted by knocking out several outer ring nucleoporins. Thus, Heh2’s association with NPCs depends on the structural integrity of both major NPC scaffold complexes. We propose a model in which Heh2 acts as a sensor of NPC assembly state, which may be important for NPC quality control mechanisms and the segregation of NPCs during cell division.

scholarly journals Heh2/Man1 may be an evolutionarily conserved sensor of NPC assembly state

2020 ◽  
Author(s):  
Sapan Borah ◽  
David J. Thaller ◽  
Zhanna Hakhverdyan ◽  
Elisa C. Rodriguez ◽  
Michael P. Rout ◽  
...  
Keyword(s):  
Protein Function ◽  
Structural Integrity ◽  
Integral Membrane Proteins ◽  
Interaction Networks ◽  
Nuclear Pore ◽  
Control Mechanisms ◽  
Winged Helix ◽  
Biochemical Interaction ◽  
Evolutionarily Conserved ◽  
Ring Complex

AbstractIntegral membrane proteins of the Lap2-emerin-MAN1 (LEM) family have emerged as important components of the inner nuclear membrane (INM) required for the functional and physical integrity of the nuclear envelope. However, like many INM proteins, there is limited understanding of the biochemical interaction networks that enable LEM protein function. Here, we show that Heh2/Man1 can be affinity purified with major scaffold components of the nuclear pore complex (NPC), specifically the inner ring complex, in evolutionarily distant yeasts. Interactions between Heh2 and nucleoporins is mediated by its C-terminal winged-helix (WH) domain and are distinct from interactions required for INM targeting. Disrupting interactions between Heh2 and the NPC leads to NPC clustering. Interestingly, Heh2’s association with NPCs can also be broken by knocking out Nup133, a component of the outer ring that does not physically interact with Heh2. Thus, Heh2’s association with NPCs depends on the structural integrity of both major NPC scaffold complexes. We propose a model in which Heh2 acts as a sensor of NPC assembly state, which may be important for NPC quality control mechanisms and the segregation of NPCs during cell division.

scholarly journals Calcineurin homologous protein: a multifunctional Ca2+-binding protein family

2012 ◽  
Vol 303 (2) ◽  
pp. F165-F179 ◽  
Author(s):  
Francesca Di Sole ◽  
Komal Vadnagara ◽  
Orson W. Moe ◽  
Victor Babich
Keyword(s):  
Protein Function ◽  
Calcium Binding ◽  
Nuclear Export ◽  
Binding Protein ◽  
Protein A ◽  
Structural Features ◽  
Homologous Protein ◽  
Evolutionarily Conserved ◽  
Ef Hand ◽  
Significant Homology

The calcineurin homologous protein (CHP) belongs to an evolutionarily conserved Ca2+-binding protein subfamily. The CHP subfamily is composed of CHP1, CHP2, and CHP3, which in vertebrates share significant homology at the protein level with each other and between other Ca2+-binding proteins. The CHP structure consists of two globular domains containing from one to four EF-hand structural motifs (calcium-binding regions composed of two helixes, E and F, joined by a loop), the myristoylation, and nuclear export signals. These structural features are essential for the function of the three members of the CHP subfamily. Indeed, CHP1–CHP3 have multiple and diverse essential functions, ranging from the regulation of the plasma membrane Na+/H+exchanger protein function, to carrier vesicle trafficking and gene transcription. The diverse functions attributed to the CHP subfamily rendered an understanding of its action highly complex and often controversial. This review provides a comprehensive and organized examination of the properties and physiological roles of the CHP subfamily with a view to revealing a link between CHP diverse functions.

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