Biology subjects

Nolte, S.

Publications and source records attributed to Nolte, S..

4 recordsLinked to original sources

bioRxiv2026

SorCS2 controls Wnt signaling homeostasis during neurodevelopment by regulating Ror2 activity and trafficking

Wnt signaling orchestrates key developmental processes, yet mechanisms restricting its spatial and temporal activity remain incompletely understood. Here we identify SorCS2, a VPS10p-domain sorting receptor, as a conserved regulator of Wnt signaling homeostasis. Integrating proteomics, cell biology, embryology, and vertebrate models, we show that SorCS2 interacts with the noncanonical Wnt receptor Ror2 and controls its trafficking, Wnt5a-induced internalization, and lysosomal degradation. In mouse dopaminergic progenitors, SorCS2 deficiency enhances responsiveness to canonical and noncanonical Wnt ligands, increases Ror2 phosphorylation, and amplifies downstream signaling of both Wnt signaling cascades. Loss of SorCS2 further disrupts the ligand-receptor feedback loop, leading to elevated Ror2, Wnt5a, and Wnt1 expression, accelerated proliferation and neurogenesis, and increased expression of Tcf4, a gene implicated in neuropsychiatric disorders. Across vertebrate systems, SorCS2-dependent control of Ror2 signaling is required for anterior-posterior axis elongation, convergent extension, somitogenesis, and brain morphogenesis. These findings define a SorCS2-dependent sorting mechanism that fine-tunes morphogen receptor signaling during vertebrate neurodevelopment.

developmental biology↗

bioRxiv2023

SorCS2 binds progranulin and regulates motor axon outgrowth

Motor neuron development requires an orchestrated action of trophic factors and guidance cues for axons to reach their targets. Here, we identify SorCS2 as a novel receptor for progranulin (PGRN) that is required for motor axon outgrowth in zebrafish and mice. In both species motor neurons express SorCS2, and PGRN is produced in cells juxta-positioned the projecting axon, but in mice the neurons also co-express PGRN. In zebrafish, sorcs2 knockdown produces stunted and aberrantly branched motor axons, and in Sorcs2-/- mice, forelimb innervation and motor neuron regeneration are substantially perturbed; phenotypes also observed in fish and mice lacking PGRN. SorCS2 binds PGRN and while motor neuron cultures from wildtype mice respond to exogenous PGRN by axon outgrowth, knockout neurons are unresponsive. Remarkably, when co-expressed in the same cells, SorCS2 controls secretion of PGRN. We conclude that SorCS2 navigates motor neuron development and enables axon regeneration through binding of PGRN.

developmental biology↗

bioRxiv2020

Amyloid precursor protein causes fusion of promyelocytic leukemia nuclear bodies in human hippocampal areas with high plaque load

The amyloid precursor protein (APP) is a type I transmembrane protein with unknown physiological function but potential impact in neurodegeneration. The current study demonstrates that APP signals to the nucleus causing the generation of aggregates comprising its adapter protein FE65 and the tumour suppressor proteins p53 and PML. The PML nuclear body generation, known to be of relevance in virus defence and cell division, is induced and fusion occurs over time depending on APP signalling. We further show that the nuclear aggregates of APP C-terminal (APP-CT) fragments together with PML and FE65 are present in the aged human brain but not in cerebral organoids differentiated from iPS cells. Notably, human Alzheimers disease brains reveal a highly significant loss of these nuclear aggregates in areas with high plaque load compared to plaque-free areas of the same individual. Based on these results we conclude that APP-CT signalling to the nucleus takes place in the aged human brain and is potentially involved in the pathophysiology of AD. Taken the current knowledge on PML bodies into account, we hypothesize a new role for APP as a twofold virus response protein. The APP-dependent defence strategy includes A{beta}-virus interaction at the extracellular matrix and APP-CT driven PML aggregation in the nucleus to encapsulate the viral nucleic acid. This defence strategy preferentially occurs in high-plaque regions of the human brain and overstimulation of this pathway results in a pyrrhic victory.

neuroscience↗

bioRxiv2019

Late-season surveys to document seed rain potential of Palmer amaranth (Amaranthus palmeri) and waterhemp (Amaranthus tuberculatus) in Texas cotton

Despite the best weed control efforts, weed escapes are often present in large production fields prior to harvest, contributing to seed rain and species persistence. Late-season surveys were conducted in cotton (Gossypium hirsutum L.) fields in Texas in 2016 and 2017 to identify common weed species present as escapes and estimate seed rain potential of Palmer amaranth (Amaranthus palmeri S. Watson) and waterhemp [A. tuberculatus (Moq.) J.D. Sauer], two troublesome weed species with high fecundity. A total of 400 cotton fields across four major cotton-producing regions in Texas [High Plains (HP), Gulf Coast (GC), Central Texas, and Blacklands] were surveyed. Results have revealed that A. palmeri, Texas millet [Urochloa texana (Buckley) R. Webster], A. tuberculatus, ragweed parthenium (Parthenium hysterophorus L.), and barnyardgrass [Echinochloa crus-galli (L.) P. Beauv.] were the top five weed escapes present in cotton fields. Amaranthus palmeri was the most prevalent weed in the HP and Lower GC regions, whereas A. tuberculatus escapes were predominantly observed in the Upper GC and Blacklands regions. On average, 9.4% of an individual field was infested with A. palmeri escapes in the Lower GC region; however, it ranged between 5.1 and 8.1% in the HP region. Average A. palmeri density ranged from 405 (Central Texas) to 3,543 plants ha-1 (Lower GC). The greatest seed rain potential by A. palmeri escapes was observed in the upper HP region (13.9 million seeds ha-1), whereas the seed rain potential of A. tuberculatus escapes was the greatest in the Blacklands (12.9 million seeds ha-1) and the upper GC regions (9.8 million seeds ha-1). Results indicated that seed rain from late-season A. palmeri and A. tuberculatus escapes are significant in Texas cotton, and effective management of these escapes is imperative for minimizing seedbank inputs and impacting species persistence.

plant biology↗