A5013255287- Genetic and Kidney Cyst Diseases
- Hedgehog Signaling Pathway Studies
- Extracellular vesicles in disease
- Cell Adhesion Molecules Research
- Microtubule and mitosis dynamics
- Renal and related cancers
- Protist diversity and phylogeny
- Genetic Syndromes and Imprinting
- RNA Interference and Gene Delivery
- Cellular transport and secretion
- Epigenetics and DNA Methylation
- RNA Research and Splicing
- Genetics and Neurodevelopmental Disorders
- Retinal Development and Disorders
- Genomics and Chromatin Dynamics
- Polyamine Metabolism and Applications
- Genomic variations and chromosomal abnormalities
- Erythrocyte Function and Pathophysiology
- Amino Acid Enzymes and Metabolism
- Congenital heart defects research
- Tuberous Sclerosis Complex Research
- Advanced Proteomics Techniques and Applications
- Micro and Nano Robotics
- Developmental Biology and Gene Regulation
- Ubiquitin and proteasome pathways
Centre for Biomedical Network Research on Rare Diseases
2021-2024
Instituto de Salud Carlos III
2021-2024
Hospital Universitario La Paz
2020-2024
Instituto de Investigaciones Biomédicas Sols-Morreale
2016-2024
Hospital La Paz Institute for Health Research
2019-2024
Consejo Superior de Investigaciones Científicas
2020-2023
Universidad Autónoma de Madrid
2016-2023
Instituto de Investigación de Enfermedades Raras
2022
Centro de Investigación Biomédica en Red
2022
Institut d'Investigació Biomédica de Bellvitge
2004-2020
Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by hamartoma formation in various organs. Two genes responsible for the disease, TSC1 and TSC2, have been identified. The TSC2 proteins, also called hamartin tuberin, respectively, shown to regulate cell growth through inhibition of mammalian target rapamycin pathway. known stabilize forming a with which GTPase-activating protein Rheb small GTPase. We identified HERC1 as TSC2-interacting protein. 532-kDa E3...
BackgroundAlthough human embryonic stem cells (hESCs) hold great promise as a source of differentiated to treat several diseases, many obstacles still need be surmounted before this can become reality. First among these, robust chemically-defined system expand hESCs in culture is unavailable despite recent advances the understanding factors controlling hESC self-renewal.Methodology/Principal FindingsIn study, we attempted find new molecules that stimulate long term self-renewal. In order do...
Cilia have a unique diffusion barrier (“gate”) within their proximal region, termed transition zone (TZ), that compartmentalises signalling proteins the organelle. The TZ is known to harbour two functional modules/complexes (Meckel syndrome [MKS] and Nephronophthisis [NPHP]) defined by genetic interaction, interdependent protein localisation (hierarchy), proteomic studies. However, composition molecular organisation of these modules links human ciliary disease are not completely understood....
The Meckel syndrome (MKS) complex functions at the transition zone, located between basal body and axoneme, to regulate localization of ciliary membrane proteins. We investigated role Tmem231, a two-pass transmembrane protein, in MKS formation function. Consistent with zone function, mutation mouse Tmem231 disrupts proteins including Arl13b Inpp5e cilia, resulting phenotypes characteristic such as polydactyly kidney cysts. B9d1 are essential for each other components Mks1 localize zone. As...
Mutations in genes encoding cilia proteins cause human ciliopathies, diverse disorders affecting many tissues. Individual can be linked to ciliopathies with dramatically different phenotypes, suggesting that genetic modifiers may participate their pathogenesis. The ciliary transition zone contains two protein complexes affected the Meckel syndrome (MKS) and nephronophthisis (NPHP). BBSome is a third complex, ciliopathy Bardet-Biedl (BBS). We tested whether mutations MKS, NPHP BBS complex...
G protein-coupled receptors (GPCRs) are the most common pharmacological target in human clinical practice. To perform their functions, many GPCRs must accumulate inside primary cilia, microtubule-based plasma membrane protrusions working as cellular antennae. Nevertheless, molecular mechanisms underlying GPCR ciliary targeting remain poorly understood. Serotonin receptor 6 (HTR6) and somatostatin 3 (SSTR3) two brain-enriched involved cognition pathologies such Alzheimer's disease cancer....
Primary cilia are sensory membrane protrusions whose dysfunction causes ciliopathies. INPP5E is a ciliary phosphoinositide phosphatase mutated in ciliopathies like Joubert syndrome. regulates numerous functions, but how it accumulates remains poorly understood. Herein, we show targeting requires its folded catalytic domain and controlled by four conserved localization signals (CLSs): LLxPIR motif (CLS1), W383 (CLS2), FDRxLYL (CLS3) CaaX box (CLS4). We answer two long-standing questions the...
HERC proteins are characterized by having one or more RCC1‐like domains as well a C‐terminal HECT domain in their amino acid sequences. This has led researchers to suggest that they may act both guanine nucleotide exchange factors and E3 ubiquitin ligases. Here we describe physical interaction between the of HERC1, giant protein involved intracellular membrane traffic, M2 isoform glycolytic enzyme pyruvate kinase (M2‐PK). Partial colocalization endogenous was observed immunofluorescence...
Abstract The transcription factor NRF2 is a master regulator of cellular antioxidant and detoxification responses, but it also regulates other processes such as autophagy pluripotency. In human embryonic stem cells (hESCs), antagonizes neuroectoderm differentiation, which only occurs after repressed via Primary Cilia-Autophagy-NRF2 (PAN) axis. However, the functional connections between primary cilia, microtubule-based plasma membrane protrusions that function antennae, remain poorly...
Abstract To be able to separate and analyze giant proteins small in the same electrophoretic gel, we have used a continuous SDS‐PAGE gel formed by combination of low‐percentage acrylamide gradient that named LAG gel. get good resolution for more than 200 kDa, an acrylamide/bisacrylamide ratio 80:1 successfully resolve 5–200 kDa range, conventional 6–15% with standard 40:1. We show system can general applications electrophoresis such as proteomics immunobloting techniques. Thus, using this it...
Abstract HERC1 is a ubiquitin ligase protein, which, when mutated, induces several malformations and intellectual disability in humans. The animal model of mutation the mouse tambaleante characterized by: (1) overproduction protein; (2) cerebellar Purkinje cells death by autophagy; (3) dysregulation autophagy spinal cord motor neurons, CA3 neocortical pyramidal neurons; (4) impairment associative learning, linked to altered spinogenesis absence LTP lateral amygdala; and, (5) due delayed...
Cilia are hair-like projections of the plasma membrane with an inner microtubule skeleton known as axoneme. Motile cilia and flagella beat to displace extracellular fluids, playing important roles in airways reproductive system. On contrary, primary function cell-type-dependent sensory organelles, detecting chemical, mechanical, or optical signals from environment. dysfunction is associated genetic diseases called ciliopathies some types cancer. have been recently identified zebrafish...
HERC1 is a giant multidomain protein involved in membrane trafficking through its interaction with vesicle coat proteins such as clathrin and ARF. Previously, it has been shown that the RCC1‐like domain 1 (RLD1) of stimulates guanine nucleotide dissociation on ARF1 Rab proteins. In this study, we have analyzed whether may also regulate ARF6 activity. We show HERC1, RLD1, GDP release from but, unexpectedly, inhibits GDP/GTP exchange under conditions where ARNO it. Furthermore, demonstrate...
We analyzed here how formin-like 1 β (FMNL1β), an actin cytoskeleton-regulatory protein, regulates microtubule-organizing center (MTOC) and multivesicular bodies (MVB) polarization exosome secretion at immune synapse (IS) model in a phosphorylation-dependent manner. IS formation was associated with transient recruitment of FMNL1β to the IS, which independent protein kinase C δ (PKCδ). Simultaneous RNA interference all FMNL1 isoforms prevented MTOC/MVB secretion, were restored by FMNL1βWT...