TY  - JOUR
A1  - Gao, Shiqiang
A1  - Nagpal, Jatin
A1  - Schneider, Martin W.
A1  - Kozjak-Pavlovic, Vera
A1  - Nagel, Georg
A1  - Gottschalk, Alexander
T1  - Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp
JF  - Nature Communications
N2  - Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. In sensory neurons, cGMP permits signal modulation, amplification and encoding, before depolarization. Here we implement a guanylyl cyclase rhodopsin from Blastocladiella emersonii as a new optogenetic tool (BeCyclOp), enabling rapid light-triggered cGMP increase in heterologous cells (Xenopus oocytes, HEK293T cells) and in Caenorhabditis elegans. Among five different fungal CyclOps, exhibiting unusual eight transmembrane topologies and cytosolic N-termini, BeCyclOp is the superior optogenetic tool (light/dark activity ratio: 5,000; no cAMP production; turnover (20 °C) ~17 cGMPs\(^{-1}\)). Via co-expressed CNG channels (OLF in oocytes, TAX-2/4 in C. elegans muscle), BeCyclOp photoactivation induces a rapid conductance increase and depolarization at very low light intensities. In O\(_2\)/CO\(_2\) sensory neurons of C. elegans, BeCyclOp activation evokes behavioural responses consistent with their normal sensory function. BeCyclOp therefore enables precise and rapid optogenetic manipulation of cGMP levels in cells and animals.
KW  - carbon dioxide avoidance
KW  - III adenylyl cyclases
KW  - rhodopsin
KW  - in vivo
KW  - optical control
KW  - Halobacterium halobium
KW  - C. elegans
KW  - cellular camp
KW  - Caenorhabditis elegans
KW  - nucleotide-gated channel
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-148197
VL  - 6
IS  - 8046
ER  - 
TY  - JOUR
A1  - Markert, Sebastian M.
A1  - Skoruppa, Michael
A1  - Yu, Bin
A1  - Mulcahy, Ben
A1  - Zhen, Mai
A1  - Gao, Shangbang
A1  - Sendtner, Michael
A1  - Stigloher, Christian
T1  - Overexpression of an ALS-associated FUS mutation in C. elegans disrupts NMJ morphology and leads to defective neuromuscular transmission
JF  - Biology Open
N2  - The amyotrophic lateral sclerosis (ALS) neurodegenerative disorder has been associated with multiple genetic lesions, including mutations in the gene for fused in sarcoma (FUS), a nuclear-localized RNA/DNA-binding protein. Neuronal expression of the pathological form of FUS proteins in Caenorhabditis elegans results in mislocalization and aggregation of FUS in the cytoplasm, and leads to impairment of motility. However, the mechanisms by which the mutant FUS disrupts neuronal health and function remain unclear. Here we investigated the impact of ALS-associated FUS on motor neuron health using correlative light and electron microscopy, electron tomography, and electrophysiology. We show that ectopic expression of wild-type or ALS-associated human FUS impairs synaptic vesicle docking at neuromuscular junctions. ALS-associated FUS led to the emergence of a population of large, electron-dense, and filament-filled endosomes. Electrophysiological recording revealed reduced transmission from motor neurons to muscles. Together, these results suggest a pathological effect of ALS-causing FUS at synaptic structure and function organization.
KW  - C. elegans
KW  - fused in sarcoma
KW  - amyotrophic lateral sclerosis
KW  - uper-resolution array tomography
KW  - electron tomography
KW  - neuromuscular junction
Y1  - 2020
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-230662
VL  - 9
ER  - 
TY  - JOUR
A1  - Link, Jana
A1  - Paouneskou, Dimitra
A1  - Velkova, Maria
A1  - Daryabeigi, Anahita
A1  - Laos, Triin
A1  - Labella, Sara
A1  - Barroso, Consuelo
A1  - Pacheco Piñol, Sarai
A1  - Montoya, Alex
A1  - Kramer, Holger
A1  - Woglar, Alexander
A1  - Baudrimont, Antoine
A1  - Markert, Sebastian Mathias
A1  - Stigloher, Christian
A1  - Martinez-Perez, Enrique
A1  - Dammermann, Alexander
A1  - Alsheimer, Manfred
A1  - Zetka, Monique
A1  - Jantsch, Verena
T1  - Transient and Partial Nuclear Lamina Disruption Promotes Chromosome Movement in Early Meiotic Prophase
JF  - Developmental Cell
N2  - Meiotic chromosome movement is important for the pairwise alignment of homologous chromosomes, which is required for correct chromosome segregation. Movement is driven by cytoplasmic forces, transmitted to chromosome ends by nuclear membrane-spanning proteins. In animal cells, lamins form a prominent scaffold at the nuclear periphery, yet the role lamins play in meiotic chromosome movement is unclear. We show that chromosome movement correlates with reduced lamin association with the nuclear rim, which requires lamin phosphorylation at sites analogous to those that open lamina network crosslinks in mitosis. Failure to remodel the lamina results in delayed meiotic entry, altered chromatin organization, unpaired or interlocked chromosomes, and slowed chromosome movement. The remodeling kinases are delivered to lamins via chromosome ends coupled to the nuclear envelope, potentially enabling crosstalk between the lamina and chromosomal events. Thus, opening the lamina network plays a role in modulating contacts between chromosomes and the nuclear periphery during meiosis.
KW  - meiosis
KW  - C. elegans
KW  - chromosome movement
KW  - chromosome pairing
KW  - nuclear envelope
KW  - lamin
Y1  - 2018
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-236901
VL  - 45
ER  -