Alternative cell fate choice induced by low-level expression of a regulator of protein phosphatase 2A in the Drosophila peripheral nervous system

Development ◽  
1994 ◽  
Vol 120 (6) ◽  
pp. 1591-1599 ◽  
Author(s):  
K. Shiomi ◽  
M. Takeichi ◽  
Y. Nishida ◽  
Y. Nishi ◽  
T. Uemura
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Cell Fate ◽  
Protein Phosphatase ◽  
Regulatory Subunit ◽  
Loss Of Function ◽  
B Subunit ◽  
Accessory Cells ◽  
Phosphatase 2A ◽  
Altered Cell

The Drosophila gene twins encodes the regulatory B subunit of type 2A protein phosphatase. Here we report that its partial loss-of-function mutations caused abnormal morphogenesis in the adult peripheral nervous system. In wild-type flies, the mechanoreceptor, one major class of sensory organs, is composed of four specialized cells (one neuron and three accessory cells) that are derived from a single precursor cell. The hypomorphic twins mutations did not block division of this precursor, but most likely altered cell fate in this lineage to produce only accessory cells that form sensory structures. Stepwise reductions of twins protein enhanced this transformation. In these mutants, another regulatory subunit, A, and the catalytic subunit, C, of the phosphatase were expressed at normal levels. Therefore, the modulation of the phosphatase activity by the B subunit appears to be crucial for specification of neural cell identity.

scholarly journals Cdc55p-Mediated E4orf4 Growth Inhibition in Saccharomyces cerevisiae Is Mediated Only in Part via the Catalytic Subunit of Protein Phosphatase 2A

2008 ◽  
Vol 82 (7) ◽  
pp. 3612-3623 ◽  
Author(s):  
Yikun Li ◽  
Huijun Wei ◽  
Tung-Chin Hsieh ◽  
David C. Pallas
Keyword(s):  
Saccharomyces Cerevisiae ◽  
Growth Inhibition ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Point Mutations ◽  
Regulatory Subunit ◽  
Stable Complex ◽  
B Subunit ◽  
C Subunit ◽  
Phosphatase 2A

ABSTRACT The adenovirus early region 4 open reading frame 4 (E4orf4) protein specifically induces p53-independent cell death of transformed but not normal human cells, suggesting that elucidation of its mechanism may provide important new avenues for cancer therapy. Wild-type E4orf4 and mutants that retain cancer cell toxicity also induce growth inhibition in Saccharomyces cerevisiae, which provides a genetically tractable system for studying E4orf4 function. Interaction with the protein phosphatase 2A (PP2A) B regulatory subunit is required for E4orf4's effects, suggesting that E4orf4 may function by regulating B subunit-containing heterotrimeric PP2A holoenzymes (PP2ABAC), which consist of a B subunit complexed with the PP2A structural (A) and catalytic (C) subunits. However, it is not known whether E4orf4-induced growth inhibition requires interaction with the PP2A C subunit or whether E4orf4 might have PP2A B subunit-dependent effects that are independent of PP2ABAC holoenzyme formation. To test these possibilities in S. cerevisiae, we disrupted the stable formation of PP2ABAC heterotrimers and thus E4orf4/C subunit association by PP2A C subunit point mutations or by deletion of the gene for the PP2A methyltransferase, Ppm1p, and assayed for effects on E4orf4-induced growth inhibition. Our results support a model in which E4orf4 mediates growth inhibition and cell killing both through PP2ABAC heterotrimers and through a B regulatory subunit-dependent pathway(s) that is independent of stable complex formation with the PP2A C subunit. They also indicate that Ppm1p has a function other than regulating the assembly of PP2A heterotrimers and suggest that selective PP2A trimer inhibitors and PP6 inhibitors may be useful as adjuvant anticancer therapies.

scholarly journals Protein phosphatase 2A is crucial for sarcomere organization in Caenorhabditis elegans striated muscle

2018 ◽  
Vol 29 (17) ◽  
pp. 2084-2097 ◽  
Author(s):  
Hiroshi Qadota ◽  
Yohei Matsunaga ◽  
Pritha Bagchi ◽  
Karen I. Lange ◽  
Karma J. Carrier ◽  
...  
Keyword(s):  
Caenorhabditis Elegans ◽  
Protein Phosphatase ◽  
Striated Muscle ◽  
Muscle Protein ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunit ◽  
Loss Of Function ◽  
Double Line ◽  
Regulatory Subunits ◽  
Phosphatase 2A

Protein phosphatase 2A (PP2A) is a heterotrimer composed of single catalytic and scaffolding subunits and one of several possible regulatory subunits. We identified PPTR-2, a regulatory subunit of PP2A, as a binding partner for the giant muscle protein UNC-89 (obscurin) in Caenorhabditis elegans. PPTR-2 is required for sarcomere organization when its paralogue, PPTR-1, is deficient. PPTR-2 localizes to the sarcomere at dense bodies and M-lines, colocalizing with UNC-89 at M-lines. PP2A components in C. elegans include one catalytic subunit LET-92, one scaffolding subunit (PAA-1), and five regulatory subunits (SUR-6, PPTR-1, PPTR-2, RSA-1, and CASH-1). In adult muscle, loss of function in any of these subunits results in sarcomere disorganization. rsa-1 mutants show an interesting phenotype: one of the two myosin heavy chains, MHC A, localizes as closely spaced double lines rather than single lines. This “double line” phenotype is found in rare missense mutants of the head domain of MHC B myosin, such as unc-54(s74). Analysis of phosphoproteins in the unc-54(s74) mutant revealed two additional phosphoserines in the nonhelical tailpiece of MHC A. Antibodies localize PPTR-1, PAA-1, and SUR-6 to I-bands and RSA-1 to M-lines and I-bands. Therefore, PP2A localizes to sarcomeres and functions in the assembly or maintenance of sarcomeres.

The Drosophila sanpodo gene controls sibling cell fate and encodes a tropomodulin homolog, an actin/tropomyosin-associated protein

Development ◽  
1998 ◽  
Vol 125 (10) ◽  
pp. 1845-1856 ◽  
Author(s):  
C.A. Dye ◽  
J.K. Lee ◽  
R.C. Atkinson ◽  
R. Brewster ◽  
P.L. Han ◽  
...  
Keyword(s):  
Nervous System ◽  
Embryonic Development ◽  
Notch Signaling ◽  
Peripheral Nervous System ◽  
Cell Fate ◽  
Genetic Interaction ◽  
Cell Fate Determination ◽  
Loss Of Function ◽  
Protein Loss ◽  
Sensory Structures

Notch signaling is required in many invertebrate and vertebrate cells to promote proper cell fate determination. Mutations in sanpodo cause many different neuronal peripheral nervous system precursor cells to generate two identical daughter neurons, instead of a neuron and sibling cell. This phenotype is similar to that observed when Notch function is lost late in embryonic development and opposite to the numb loss-of-function phenotype. Genetic interaction studies show that sanpodo is epistatic to numb. sanpodo encodes a homolog of tropomodulin, an actin/tropomyosin-associated protein. Loss of sanpodo leads to an aberrant F-actin distribution and causes differentiation defects of actin-containing sensory structures. Our data suggest that an actin-based process is involved in Notch signaling.

Differential Expression of three Arabidopsis Genes Encoding the B' Regulatory Subunit of Protein Phosphatase 2A

1997 ◽  
Vol 245 (1) ◽  
pp. 156-163 ◽  
Author(s):  
Keith A. Latorre ◽  
Darby M. Harris ◽  
Sabine J. Rundle
Keyword(s):  
Differential Expression ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunit ◽  
Genes Encoding ◽  
Phosphatase 2A

scholarly journals A Gain-of-Function Screen for Genes That Affect the Development of the Drosophila Adult External Sensory Organ

Genetics ◽  
2000 ◽  
Vol 155 (2) ◽  
pp. 733-752 ◽  
Author(s):  
Salim Abdelilah-Seyfried ◽  
Yee-Ming Chan ◽  
Chaoyang Zeng ◽  
Nicholas J Justice ◽  
Susan Younger-Shepherd ◽  
...  
Keyword(s):  
Nervous System ◽  
Peripheral Nervous System ◽  
Cell Fate ◽  
P Element ◽  
External Support ◽  
Sensory Organ ◽  
Sensory Organs ◽  
Gain Of Function ◽  
Asymmetric Cell Divisions ◽  
Single Precursor

Abstract The Drosophila adult external sensory organ, comprising a neuron and its support cells, is derived from a single precursor cell via several asymmetric cell divisions. To identify molecules involved in sensory organ development, we conducted a tissue-specific gain-of-function screen. We screened 2293 independent P-element lines established by P. Rørth and identified 105 lines, carrying insertions at 78 distinct loci, that produced misexpression phenotypes with changes in number, fate, or morphology of cells of the adult external sensory organ. On the basis of the gain-of-function phenotypes of both internal and external support cells, we subdivided the candidate lines into three classes. The first class (52 lines, 40 loci) exhibits partial or complete loss of adult external sensory organs. The second class (38 lines, 28 loci) is associated with increased numbers of entire adult external sensory organs or subsets of sensory organ cells. The third class (15 lines, 10 loci) results in potential cell fate transformations. Genetic and molecular characterization of these candidate lines reveals that some loci identified in this screen correspond to genes known to function in the formation of the peripheral nervous system, such as big brain, extra macrochaetae, and numb. Also emerging from the screen are a large group of previously uncharacterized genes and several known genes that have not yet been implicated in the development of the peripheral nervous system.

scholarly journals Structure and expression of a 72-kDa regulatory subunit of protein phosphatase 2A. Evidence for different size forms produced by alternative splicing

1993 ◽  
Vol 268 (20) ◽  
pp. 15267-15276
Author(s):  
P. Hendrix ◽  
R.E. Mayer-Jackel ◽  
P. Cron ◽  
J. Goris ◽  
J. Hofsteenge ◽  
...  
Keyword(s):  
Alternative Splicing ◽  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunit ◽  
Phosphatase 2A

scholarly journals Regulatory Subunit B′γ of Protein Phosphatase 2A Prevents Unnecessary Defense Reactions under Low Light in Arabidopsis

2011 ◽  
Vol 156 (3) ◽  
pp. 1464-1480 ◽  
Author(s):  
Andrea Trotta ◽  
Michael Wrzaczek ◽  
Judith Scharte ◽  
Mikko Tikkanen ◽  
Grzegorz Konert ◽  
...  
Keyword(s):  
Protein Phosphatase ◽  
Protein Phosphatase 2A ◽  
Regulatory Subunit ◽  
Low Light ◽  
Defense Reactions ◽  
Phosphatase 2A ◽  
Subunit B
Sign in / Sign up

Export Citation Format

Share Document