Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche

Michel, Marcus; Raabe, Isabel; Kupinski, Adam P.; Pérez-Palencia, Raquel; Bökel, Christian

doi:10.1038/ncomms1426

Cited by 93 publications

(112 citation statements)

References 59 publications

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“…In the ventricular region of the developing brain N-cadherin is required for maintaining NSCs by preventing differentiation via regulation of Akt signaling (Zhang et al, 2010). Finally, in the Drosophila testis, BMP receptor complexes are localized to Ecadherin-rich AJs at the stem cell-niche junction, which might help restrict BMP signaling activity to the GSC niche (Michel et al, 2011). These lines of evidence support a role for cadherins in the regulation of cell signaling pathways important for stem cell selfrenewal and proliferation (Fig.…”

Section: Controlling Stem Cell Self-renewal Via Signalingmentioning

confidence: 74%

Adhesion in the stem cell niche: biological roles and regulation

2013

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Stem cell self-renewal is tightly controlled by the concerted action of stem cell-intrinsic factors and signals within the niche. Niche signals often function within a short range, allowing cells in the niche to self-renew while their daughters outside the niche differentiate. Thus, in order for stem cells to continuously self-renew, they are often anchored in the niche via adhesion molecules. In addition to niche anchoring, however, recent studies have revealed other important roles for adhesion molecules in the regulation of stem cell function, and it is clear that stem cell-niche adhesion is crucial for stem cell self-renewal and is dynamically regulated. Here, we highlight recent progress in understanding adhesion between stem cells and their niche and how this adhesion is regulated.

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Section: Controlling Stem Cell Self-renewal Via Signalingmentioning

confidence: 74%

Adhesion in the stem cell niche: biological roles and regulation

2013

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“…BMP signaling complexes are thought to function in this manner in the maintenance of stemness (Michel et al, 2011) and in epithelial-tomesenchymal transition (Zeisberg et al, 2003).…”

Section: Possible Functions For Synaptic Pmadmentioning

confidence: 99%

Postsynaptic glutamate receptors regulate local BMP signaling at theDrosophilaneuromuscular junction

2014

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Effective communication between pre-and postsynaptic compartments is required for proper synapse development and function. At the Drosophila neuromuscular junction (NMJ), a retrograde BMP signal functions to promote synapse growth, stability and homeostasis and coordinates the growth of synaptic structures. Retrograde BMP signaling triggers accumulation of the pathway effector pMad in motoneuron nuclei and at synaptic termini. Nuclear pMad, in conjunction with transcription factors, modulates the expression of target genes and instructs synaptic growth; a role for synaptic pMad remains to be determined. Here, we report that pMad signals are selectively lost at NMJ synapses with reduced postsynaptic sensitivities. Despite this loss of synaptic pMad, nuclear pMad persisted in motoneuron nuclei, and expression of BMP target genes was unaffected, indicating a specific impairment in pMad production/maintenance at synaptic termini. During development, synaptic pMad accumulation followed the arrival and clustering of ionotropic glutamate receptors (iGluRs) at NMJ synapses. Synaptic pMad was lost at NMJ synapses developing at suboptimal levels of iGluRs and Neto, an auxiliary subunit required for functional iGluRs. Genetic manipulations of non-essential iGluR subunits revealed that synaptic pMad signals specifically correlated with the postsynaptic type-A glutamate receptors. Altering type-A receptor activities via protein kinase A (PKA) revealed that synaptic pMad depends on the activity and not the net levels of postsynaptic type-A receptors. Thus, synaptic pMad functions as a local sensor for NMJ synapse activity and has the potential to coordinate synaptic activity with a BMP retrograde signal required for synapse growth and homeostasis.

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“…In addition, BMP-Smad1 signaling controls many other aspects of development and tissue homeostasis and its dysregulation leads to the development of a number of diseases, including cancer and skeletal and vascular diseases. In addition, BMPs are present in the bloodstream and in the microenvironments of many adult stem cells, including neural stem cells, mesenchymal stem cells and skin stem cells [7,11,13]. Therefore, it is reasonable to predict that many cells encounter BMPs in vivo.…”

Section: Discussionmentioning

confidence: 99%

“…It has been reported that BMPs can stimulate cell proliferation under certain conditions [13,42]. Previous studies have also established that SXS phosphorylation is essential for Smad1 function.…”

Section: Serum Starvation Altered the Dynamics And Amplitude Of Bmp-smentioning

confidence: 99%

“…It was shown that any three alleles of Smad1 and Smad5, but not any two alleles, can support the proper development of mouse embryos [10]. In adult mice, BMPs have been shown to play critical roles in regulating the proliferation and differentiation of tissue stem cells, including neural and mesenchymal stem cells [11][12][13]. The tight regulation of BMPSmad1/5/8 signaling is physiologically important: dysregulation of this signaling has been found to result in tumor formation and the development of bone and vascular diseases [6,7,[14][15][16].…”

Section: Introductionmentioning

confidence: 99%

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Smad1 stabilization and delocalization in response to the blockade of BMP activity

Wang

Chau

et al. 2013

Cellular and Molecular Biology Letters

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Signaling at the plasma membrane receptors is generally terminated by some form of feedback regulation, such as endocytosis and/or degradation of the receptors. BMP-Smad1 signaling can also be attenuated by BMP-induced expression of the inhibitory Smads, which are negative regulators of Smad1 transactivation activity and/or BMP antagonists. Here, we report on a novel Smad1 regulation mechanism that occurs in response to the blockade of BMP activity. Lowering the serum levels or antagonizing BMPs with noggin led to upregulation of Smad1 at the protein level in several cell lines, but not to upregulation of Smad5, Smad8 or Smad2/3. The Smad1 upregulation occurs at the level of protein stabilization. Upregulated Smad1 was relocalized to the perinuclear region. These alterations seem to affect the dynamics and amplitude of BMP2-induced Smad1 reactivation. Our findings indicate that depleting or antagonizing BMPs leads to Smad1 stabilization and relocalization, thus revealing an unexpected regulatory mechanism for BMP-Smad1 signaling.

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Local BMP receptor activation at adherens junctions in the Drosophila germline stem cell niche

Cited by 93 publications

References 59 publications

Adhesion in the stem cell niche: biological roles and regulation

Adhesion in the stem cell niche: biological roles and regulation

Postsynaptic glutamate receptors regulate local BMP signaling at theDrosophilaneuromuscular junction

Smad1 stabilization and delocalization in response to the blockade of BMP activity

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