Regulated recruitment of SRGAP1 modulates RhoA signaling for contractility during epithelial junction maturation

Cytoskeleton ◽  
2017 ◽  
Vol 75 (2) ◽  
pp. 61-69 ◽  
Author(s):  
Xuan Liang ◽  
Sajini Kiru ◽  
Guillermo A. Gomez ◽  
Alpha S. Yap
2009 ◽  
Vol 1165 (1) ◽  
pp. 88-98 ◽  
Author(s):  
Sandra Citi ◽  
Serge Paschoud ◽  
Pamela Pulimeno ◽  
Francesco Timolati ◽  
Fabrizio De Robertis ◽  
...  

2010 ◽  
Vol 51 (1) ◽  
pp. 223 ◽  
Author(s):  
Patricia K. Russ ◽  
Asher I. Kupperman ◽  
Sai-Han Presley ◽  
Frederick R. Haselton ◽  
Min S. Chang

2016 ◽  
Vol 311 (5) ◽  
pp. G964-G973 ◽  
Author(s):  
Jagmohan Singh ◽  
Ettickan Boopathi ◽  
Sankar Addya ◽  
Benjamin Phillips ◽  
Isidore Rigoutsos ◽  
...  

A comprehensive genomic and proteomic, computational, and physiological approach was employed to examine the (previously unexplored) role of microRNAs (miRNAs) as regulators of internal anal sphincter (IAS) smooth muscle contractile phenotype and basal tone. miRNA profiling, genome-wide expression, validation, and network analyses were employed to assess changes in mRNA and miRNA expression in IAS smooth muscles from young vs. aging rats. Multiple miRNAs, including rno-miR-1, rno-miR-340-5p, rno-miR-185, rno-miR-199a-3p, rno-miR-200c, rno-miR-200b, rno-miR-31, rno-miR-133a, and rno-miR-206, were found to be upregulated in aging IAS. qPCR confirmed the upregulated expression of these miRNAs and downregulation of multiple, predicted targets ( Eln, Col3a1, Col1a1, Zeb2, Myocd, Srf, Smad1, Smad2, Rhoa/Rock2, Fn1, Tagln v2, Klf4, and Acta2) involved in regulation of smooth muscle contractility. Subsequent studies demonstrated an aging-associated increase in the expression of miR-133a, corresponding decreases in RhoA, ROCK2, MYOCD, SRF, and SM22α protein expression, RhoA-signaling, and a decrease in basal and agonist [U-46619 (thromboxane A2analog)]-induced increase in the IAS tone. Moreover, in vitro transfection of miR-133a caused a dose-dependent increase of IAS tone in strips, which was reversed by anti-miR-133a. Last, in vivo perianal injection of anti-miR-133a reversed the loss of IAS tone associated with age. This work establishes the important regulatory effect of miRNA-133a on basal and agonist-stimulated IAS tone. Moreover, reversal of age-associated loss of tone via anti-miR delivery strongly implicates miR dysregulation as a causal factor in the aging-associated decrease in IAS tone and suggests that miR-133a is a feasible therapeutic target in aging-associated rectoanal incontinence.


2017 ◽  
Vol 18 (10) ◽  
pp. 783-791 ◽  
Author(s):  
Xiao Huaitong ◽  
Feng Yuanyong ◽  
Tao Yueqin ◽  
Zhao Peng ◽  
Shang Wei ◽  
...  

2016 ◽  
Vol 27 (9) ◽  
pp. 1442-1450 ◽  
Author(s):  
Patrick R. O’Neill ◽  
Vani Kalyanaraman ◽  
N. Gautam

Migratory immune cells use intracellular signaling networks to generate and orient spatially polarized responses to extracellular cues. The monomeric G protein Cdc42 is believed to play an important role in controlling the polarized responses, but it has been difficult to determine directly the consequences of localized Cdc42 activation within an immune cell. Here we used subcellular optogenetics to determine how Cdc42 activation at one side of a cell affects both cell behavior and dynamic molecular responses throughout the cell. We found that localized Cdc42 activation is sufficient to generate polarized signaling and directional cell migration. The optically activated region becomes the leading edge of the cell, with Cdc42 activating Rac and generating membrane protrusions driven by the actin cytoskeleton. Cdc42 also exerts long-range effects that cause myosin accumulation at the opposite side of the cell and actomyosin-mediated retraction of the cell rear. This process requires the RhoA-activated kinase ROCK, suggesting that Cdc42 activation at one side of a cell triggers increased RhoA signaling at the opposite side. Our results demonstrate how dynamic, subcellular perturbation of an individual signaling protein can help to determine its role in controlling polarized cellular responses.


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