A5055700373- Ubiquitin and proteasome pathways
- Histone Deacetylase Inhibitors Research
- Hereditary Neurological Disorders
- Microtubule and mitosis dynamics
- Autophagy in Disease and Therapy
- Endoplasmic Reticulum Stress and Disease
- Cancer Research and Treatments
- Neurogenesis and neuroplasticity mechanisms
- Cellular Mechanics and Interactions
- RNA regulation and disease
- Neurological diseases and metabolism
- Protein Tyrosine Phosphatases
- RNA modifications and cancer
- Signaling Pathways in Disease
Tel Aviv University
2014-2022
The axonal transport of vesicles promotes microtubule acetylation across species.
The protein p27Kip1 plays roles that extend beyond cell-cycle regulation during cerebral cortex development, such as the of neuronal migration and neurite branching via signaling pathways converge on actin microtubule cytoskeletons. Microtubule-dependent transport is essential for maturation neurons establishment connectivity though synapse formation maintenance. Here, we show controls vesicles organelles along axon mice cortical projection in vitro. Moreover, suppression ortholog, dacapo,...
Abstract Microtubule (MT)-based transport is an evolutionary conserved process finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, primarily catalyzed a vesicular pool of N-acetyltransferase 1 (Atat1), promotes the recruitment and processivity molecular motors along MT tracks. However, mechanism that controls Atat1 activity remains poorly understood. Here, we show ATP-citrate lyase (Acly) enriched in vesicles provide Acetyl-Coenzyme-A (Acetyl-CoA) to Atat1. In...
A splicing mutation in the IKBKAP gene causes Familial Dysautonomia (FD), affecting IKAP protein expression levels and proper development function of peripheral nervous system (PNS). Here we found new molecular insights for role impact FD human PNS lineage by using a novel unique embryonic stem cell (hESC) line homozygous to originated pre implantation genetic diagnosis (PGD) analysis. We that downregulation during differentiation affects normal migration FD-hESC derived neural crest cells...
The splice site mutation in the IKBKAP gene coding for IKAP protein leads to tissue-specific skipping of exon 20, with concomitant reduction production. This causes neurodevelopmental, autosomal-recessive genetic disorder - Familial Dysautonomia (FD). molecular hallmark FD is severe nervous system that believed be main reason devastating symptoms this disease. Our recent studies showed brain two patients, genes linked oligodendrocyte differentiation and/or myelin formation are significantly...
The six subunits (Elp1 to Elp6) Elongator complex promotes specific uridine modifications in tRNA's wobble site. Moreover, this has been indirectly involved the regulation of α-tubulin acetylation microtubules (MTs) via stabilization ATP-Citrate Lyase (Acly), main cytosolic source acetyl-CoA production cells, a key substrate used for global protein acetylation. Here, we report additional evidence that activity is important proper cytoskeleton remodeling as cells lacking expression Elp1 show...
Microtubules are polymerized dimers of α- and β-tubulin that underlie a broad range cellular activities. Acetylation α-tubulin by the acetyl-transferase ATAT1 modulates microtubule dynamics functions in neurons. However, it remains unclear how why this enzyme acetylates microtubules over long distances axons. Here, we show loss impairs axonal transport neurons cell free motility assays confirm requirement tubulin acetylation for proper bidirectional vesicular transport. Moreover, demonstrate...
Event Abstract Back to P27kip1 is a new regulator of axonal transport Giovanni Morelli1, 2*, Aviel Even3, Juliette Godin4, Romain Le Bail2, Jean-Michel Rigo1, Bassem Hassan5, Bert Brône1 and Laurent Nguyen2* 1 UHasselt, Biomed, Belgium 2 University Liege, Giga Neuroscience, 3 Tel Aviv University, Department Cell Research Immunology, The George S. Wise Faculty for Life Sciences, Sagol School Neurosciences,, Israel 4 CNRS U7104/INSERM U964, Institut de Génétique et Biologie Moléculaire...
Abstract Microtubule (MT)-based transport is an evolutionary conserved processed finely tuned by posttranslational modifications. Among them, α-tubulin acetylation, which catalyzed the N-acetyltransferase 1, Atat1, promotes recruitment and processivity of molecular motors along MT tracks. However, mechanisms that controls Atat1 activity remains poorly understood. Here, we show a pool vesicular ATP-citrate lyase Acly acts as rate limiting enzyme to modulate controlling availability...