FGF binding proteins (FGFBPs): Modulators of FGF signaling in the developing, adult, and stressed nervous system

Taetzsch, Thomas; Brayman, Vanessa L.; Valdez, Gregorio

doi:10.1016/j.bbadis.2018.06.009

Cited by 22 publications

(23 citation statements)

References 126 publications

(132 reference statements)

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“…FGF binding proteins (FGFBPs) are secreted proteins that release locally stored FGFs from the extracellular HSPG‐rich matrix to facilitate activation of cells that express FGFRs (Figure 3) (Taetzsch et al, 2018; Tassi et al, 2011). FGFBP1 is expressed in skeletal muscle and enriched in the neuromuscular junction (NMJ).…”

Section: Regulation Of Fgfr Signal Transduction By Extracellular and ...mentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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The fibroblast growth factor (FGF) family is composed of 18 secreted signaling proteins consisting of canonical FGFs and endocrine FGFs that activate four receptor tyrosine kinases (FGFRs 1-4) and four intracellular proteins (intracellular FGFs or iFGFs) that primarily function to regulate the activity of voltagegated sodium channels and other molecules. The canonical FGFs, endocrine FGFs, and iFGFs have been reviewed extensively by us and others. In this review, we briefly summarize past reviews and then focus on new developments in the FGF field since our last review in 2015. Some of the highlights in the past 6 years include the use of optogenetic tools, viral vectors, and inducible transgenes to experimentally modulate FGF signaling, the clinical use of small molecule FGFR inhibitors, an expanded understanding of endocrine FGF signaling, functions for FGF signaling in stem cell pluripotency and differentiation, roles for FGF signaling in tissue homeostasis and regeneration, a continuing elaboration of mechanisms of FGF signaling in development, and an expanding appreciation of roles for FGF signaling in neuropsychiatric diseases.

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Section: Regulation Of Fgfr Signal Transduction By Extracellular and ...mentioning

confidence: 99%

New developments in the biology of fibroblast growth factors

Ornitz

Itoh

2022

WIREs Mechanisms of Disease

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“…These co-receptors include fibroblast growth factor receptor (FGFR) and hepatocyte growth factor receptor (HGFR) for both AAV2 and AAV3, platelet-derived growth factor receptor (PDGF) for AAV5, and epidermal growth factor receptor (EGFR) for AAV6 (Madigan and Asokan, 2016). Signaling through each of these receptors has been linked to NMJ formation/function (Zhao et al, 1999;Li et al, 2012;Taetzsch et al, 2018), consistent with their synaptic availability. Additional receptors have been identified for engineered serotypes contributing to distinct tropisms (Hordeaux et al, 2019;Huang et al, 2019).…”

Section: Adeno-associated Virusmentioning

confidence: 99%

Intramuscular Delivery of Gene Therapy for Targeting the Nervous System

Tosolini

Sleigh

2020

Front. Mol. Neurosci.

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Virus-mediated gene therapy has the potential to deliver exogenous genetic material into specific cell types to promote survival and counteract disease. This is particularly enticing for neuronal conditions, as the nervous system is renowned for its intransigence to therapeutic targeting. Administration of gene therapy viruses into skeletal muscle, where distal terminals of motor and sensory neurons reside, has been shown to result in extensive transduction of cells within the spinal cord, brainstem, and sensory ganglia. This route is minimally invasive and therefore clinically relevant for gene therapy targeting to peripheral nerve soma. For successful transgene expression, viruses administered into muscle must undergo a series of processes, including host cell interaction and internalization, intracellular sorting, long-range retrograde axonal transport, endosomal liberation, and nuclear import. In this review article, we outline key characteristics of major gene therapy viruses—adenovirus, adeno-associated virus (AAV), and lentivirus—and summarize the mechanisms regulating important steps in the virus journey from binding at peripheral nerve terminals to nuclear delivery. Additionally, we describe how neuropathology can negatively influence these pathways, and conclude by discussing opportunities to optimize the intramuscular administration route to maximize gene delivery and thus therapeutic potential.

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“…In turn, Fgfbps comprise a family of three secreted proteins that act as Fgf chaperons. Fgfbp1 is the best characterized member in Fgfbps, being shown to bind to Fgf1 and 2 (Fgf1 subfamily) and 7, 10, and 22 (Fgf7 subfamily) (Taetzsch, Brayman et al, 2018). As Fgf21 is a member of endocrine-acting Fgfs, it does not appear to require Fgfbps to reach its place of action.…”

Section: Discussionmentioning

confidence: 99%

Rac-dependent signaling from keratinocytes promotes differentiation of intradermal white adipocytes

Ueyama

Sakuma

Nakatsuji

et al. 2018

Preprint

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Rac signaling affects numerous downstream targets; however, few studies have established in vivo levels. We generated mice with a single knockout (KO) of Rac1 (Keratin5 (K5)-Cre;Rac1 flox/flox , Rac1-KO) and double KO of Rac1 and Rac3 (K5-Cre;Rac1 flox/flox ;Rac3 −/− , Rac1/Rac3-DKO) in keratinocytes. Strikingly, Rac1-KO mice exhibited thinner dermal white adipose tissue, which was considerably further reduced in Rac1/Rac3-DKO mice. DNA microarray using primary keratinocytes from Rac1/Rac3-DKO mice exhibited decreased mRNA levels of Bmp2, Bmp5, Fgf20, Fgf21, Fgfbp1, and Pdgf. Combinational treatment with BMP2 and FGF21 or BMP2 and FGF20 in culture medium, but not individual purified recombinant proteins, could differentiate 3T3-L1 fibroblasts into adipocytes, as could culture media obtained from primary keratinocytes.Conversely, addition of anti-BMP2 or anti-FGF21 antibodies into the culture medium inhibited fibroblast differentiation. Furthermore, combinational treatment with BMP2 and FGF21 promoted adipocyte differentiation only of rat primary white, but not brown, adipocyte precursors. Notably, brown adipogenesis by FGF21 was inhibited by BMP2. Thus, we proposed novel paracrine pathways from keratinocytes to intradermal pre-adipocytes, which function as Rac-dependent modulators of white adipogenesis, but also brown adipogenesis.

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FGF binding proteins (FGFBPs): Modulators of FGF signaling in the developing, adult, and stressed nervous system

Cited by 22 publications

References 126 publications

New developments in the biology of fibroblast growth factors

New developments in the biology of fibroblast growth factors

Intramuscular Delivery of Gene Therapy for Targeting the Nervous System

Rac-dependent signaling from keratinocytes promotes differentiation of intradermal white adipocytes

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