scholarly journals ERBB3-dependent AKT and ERK pathways are essential for atrioventricular cushion development in mouse embryos

PLoS ONE ◽  
2021 ◽  
Vol 16 (10) ◽  
pp. e0259426
Author(s):  
Kyoungmi Kim ◽  
Daekee Lee
Keyword(s):  
Binding Sites ◽  
Heart Development ◽  
Mesenchymal Cell ◽  
Embryonic Heart ◽  
Regulatory Subunit ◽  
Akt Pathway ◽  
Erk Activation ◽  
Binding Partner ◽  
Downstream Signaling ◽  
Heart Physiology

ERBB family members and their ligands play an essential role in embryonic heart development and adult heart physiology. Among them, ERBB3 is a binding partner of ERBB2; the ERBB2/3 complex mediates downstream signaling for cell proliferation. ERBB3 has seven consensus binding sites to the p85 regulatory subunit of PI3K, which activates the downstream AKT pathway, leading to the proliferation of various cells. This study generated a human ERBB3 knock-in mouse expressing a mutant ERBB3 whose seven YXXM p85 binding sites were replaced with YXXA. Erbb3 knock-in embryos exhibited lethality between E12.5 to E13.5, and showed a decrease in mesenchymal cell numbers and density in AV cushions. We determined that the proliferation of mesenchymal cells in the atrioventricular (AV) cushion in Erbb3 knock-in mutant embryos was temporarily reduced due to the decrease of AKT and ERK1/2 phosphorylation. Overall, our results suggest that AKT/ERK activation by the ERBB3-dependent PI3K signaling is crucial for AV cushion morphogenesis during embryonic heart development.

scholarly journals Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration

2020 ◽  
Author(s):  
Ah-Lai Law ◽  
Shamsinar Jalal ◽  
Fuad Mosis ◽  
Tommy Pallett ◽  
Ahmad Guni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Binding Sites ◽  
Leading Edge ◽  
Mesenchymal Cell ◽  
Negative Regulators ◽  
Binding Partner ◽  
Direct Binding ◽  
The Stability ◽  
Wave Complex ◽  
Lamellipodia Formation

AbstractCell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. We have identified Nance-Horan Syndrome-like 1 protein (NHSL1) as a novel, direct binding partner of the Scar/WAVE complex, which co-localise at protruding lamellipodia. This interaction is mediated by the Abi SH3 domain and two binding sites in NHSL1. Furthermore, active Rac binds to NHSL1 at two regions that mediate leading edge targeting of NHSL1 suggesting that Rac recruits NHSL1. Surprisingly, NHSL1 inhibits cell migration through its interaction with the Scar/WAVE complex. Mechanistically, NHSL1 may reduce cell migration efficiency by impeding Arp2/3 activity, as measured in cells using a novel Arp2/3 FRET-FLIM biosensor, resulting in reduced F-actin content of lamellipodia, and consequently impairing the stability of lamellipodia protrusions.

scholarly journals Nance-Horan Syndrome-like 1 protein negatively regulates Scar/WAVE-Arp2/3 activity and inhibits lamellipodia stability and cell migration

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Ah-Lai Law ◽  
Shamsinar Jalal ◽  
Tommy Pallett ◽  
Fuad Mosis ◽  
Ahmad Guni ◽  
...  
Keyword(s):  
Cell Migration ◽  
Binding Sites ◽  
Leading Edge ◽  
Mesenchymal Cell ◽  
Negative Regulators ◽  
Binding Partner ◽  
Direct Binding ◽  
The Stability ◽  
Wave Complex ◽  
Lamellipodia Formation

AbstractCell migration is important for development and its aberrant regulation contributes to many diseases. The Scar/WAVE complex is essential for Arp2/3 mediated lamellipodia formation during mesenchymal cell migration and several coinciding signals activate it. However, so far, no direct negative regulators are known. Here we identify Nance-Horan Syndrome-like 1 protein (NHSL1) as a direct binding partner of the Scar/WAVE complex, which co-localise at protruding lamellipodia. This interaction is mediated by the Abi SH3 domain and two binding sites in NHSL1. Furthermore, active Rac binds to NHSL1 at two regions that mediate leading edge targeting of NHSL1. Surprisingly, NHSL1 inhibits cell migration through its interaction with the Scar/WAVE complex. Mechanistically, NHSL1 may reduce cell migration efficiency by impeding Arp2/3 activity, as measured in cells using a Arp2/3 FRET-FLIM biosensor, resulting in reduced F-actin density of lamellipodia, and consequently impairing the stability of lamellipodia protrusions.

Optical approaches to ontogeny of electrical activity and related functional organization during early heart development

1991 ◽  
Vol 71 (1) ◽  
pp. 53-91 ◽  
Author(s):  
K. Kamino
Keyword(s):  
Electrical Activity ◽  
Heart Development ◽  
Functional Organization ◽  
Embryonic Heart ◽  
Optical Recording ◽  
Additional Advantage ◽  
Physiological Functions ◽  
Spontaneous Electrical Activity ◽  
Somite Stage ◽  
Voltage Sensitive Dyes

Direct intracellular measurement of electrical events in the early embryonic heart is impossible because the cells are too small and frail to be impaled with microelectrodes; it is also not possible to apply conventional electrophysiological techniques to the early embryonic heart. For these reasons, complete understanding of the ontogeny of electrical activity and related physiological functions of the heart during early development has been hampered. Optical signals from voltage-sensitive dyes have provided a new powerful tool for monitoring changes in transmembrane voltage in a wide variety of living preparations. With this technique it is possible to make optical recordings from the cells that are inaccessible to microelectrodes. An additional advantage of the optical method for recording membrane potential activity is that electrical activity can be monitored simultaneously from many sites in a preparation. Thus, applying a multiple-site optical recording method with a 100- or 144-element photodiode array and voltage-sensitive dyes, we have been able to monitor, for the first time, spontaneous electrical activity in prefused cardiac primordia in the early chick embryos at the six- and the early seven-somite stages of development. We were able to determine that the time of initiation of the contraction is the middle period of the nine-somite stage. In the rat embryonic heart, the onset of spontaneous electrical activity and contraction occurs at the three-somite stage. In this review, a new view of the ontogenetic sequence of spontaneous electrical activity and related physiological functions such as ionic properties, pacemaker function, conduction, and characteristics of excitation-contraction coupling in the early embryonic heart are discussed.

scholarly journals miR-1/133a Clusters Cooperatively Specify the Cardiomyogenic Lineage by Adjustment of Myocardin Levels during Embryonic Heart Development

PLoS Genetics ◽  
2013 ◽  
Vol 9 (9) ◽  
pp. e1003793 ◽  
Author(s):  
Katharina Wystub ◽  
Johannes Besser ◽  
Angela Bachmann ◽  
Thomas Boettger ◽  
Thomas Braun
Keyword(s):  
Heart Development ◽  
Embryonic Heart

scholarly journals Covalent labelling of ligand binding sites of human placental S-adenosylhomocysteine hydrolase with 8-azido derivatives of adenosine and cyclic AMP

1985 ◽  
Vol 232 (3) ◽  
pp. 643-650 ◽  
Author(s):  
V N Aiyar ◽  
M S Hershfield
Keyword(s):  
Cyclic Amp ◽  
Binding Sites ◽  
Catalytic Mechanism ◽  
Periodate Oxidation ◽  
Regulatory Subunit ◽  
Adenosylhomocysteine Hydrolase ◽  
Dependent Protein ◽  
Covalently Linked ◽  
The Relationship ◽  
Derivatives Of

S-Adenosylhomocysteine hydrolase (AdoHcyase) has previously been identified as a cytoplasmic adenosine and cyclic AMP binding protein. In order to examine the relationship between the adenosine and cyclic AMP binding sites on this enzyme we have explored the use of 8-azido analogues of adenosine and cyclic AMP as photoaffinity reagents for covalently labelling AdoHcyase purified from human placenta. 8-Azidoadenosine (8-N3-Ado), like adenosine, inactivated AdoHcyase, and the rate of inactivation was greatly increased by periodate oxidation. In addition, 8-N3-Ado was found to participate in the first step in the catalytic mechanism for AdoHcyase, resulting in conversion of enzyme-bound NAD+ to NADH, although it was not a substrate for the full enzyme-catalysed reaction. Radioactively labelled 8-N3-Ado, its periodate-oxidized derivative and 8-azidoadenosine 3′, 5′-phosphate (8-N3-cAMP) bound specifically to adenosine binding sites on AdoHcyase and, after irradiation, became covalently linked to the enzyme. Photoaffinity-labelled enzyme could be precipitated by monoclonal antibody to human AdoHcyase. Two observations suggested that cyclic AMP and adenosine bind to the same sites on AdoHcyase. First cyclic AMP and adenosine each blocked binding of both radioactively labelled 8-N3-Ado and 8-N3-cAMP, and second, digestion with V8 proteinase generated identical patterns of peptides from AdoHcyase that had been photolabelled with [32P]8-N3-cAMP and [3H]8-N3-Ado. Binding sites for cyclic AMP on AdoHcyase were found to differ functionally and structurally from cyclic AMP binding sites on the R1 regulatory subunit of cyclic AMP-dependent protein kinase.

The Na+-Ca2+ Exchanger Is Essential for Embryonic Heart Development in Mice

2000 ◽  
Vol 10 (6) ◽  
pp. 712-722 ◽  
Author(s):  
Chung-Hyun Cho ◽  
Sung Sook Kim ◽  
Myung-jin Jeong ◽  
Chin O. Lee ◽  
Hee-Sup Shin
Keyword(s):  
Heart Development ◽  
Embryonic Heart
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