Coordination of Chromosome Segregation and Cell Division in Staphylococcus aureus

Productive bacterial cell division and survival of progeny requires tight coordination between chromosome segregation and cell division to ensure equal partitioning of DNA. Unlike rod-shaped bacteria that undergo division in one plane, the coccoid human pathogen Staphylococcus aureus divides in three successive orthogonal planes, which requires a different spatial control compared to rod-shaped cells. To gain a better understanding of how this coordination between chromosome segregation and cell division is regulated in S. aureus, we investigated proteins that associate with FtsZ and the divisome. We found that DnaK, a well-known chaperone, interacts with FtsZ, EzrA and DivIVA, and is required for DivIVA stability. Unlike in several rod shaped organisms, DivIVA in S. aureus associates with several components of the divisome, as well as the chromosome segregation protein, SMC. This data, combined with phenotypic analysis of mutants, suggests a novel role for S. aureus DivIVA in ensuring cell division and chromosome segregation are coordinated

Pathogenic tau perturbs axonogenesis via loss of tau function

Neurodegenerative diseases are a major public health burden. There are only a few effective therapies because the underlying disease mechanisms are poorly understood. Tau aggregation is a hallmark of several neurodegenerative diseases, including Alzheimer’s disease and frontotemporal dementia. There are causal disease variants of the tau-encoding gene, MAPT, and the presence of tau aggregates is highly correlated with disease progression. The molecular mechanisms linking pathological tau to neuronal dysfunction are not well understood. A major challenge for the tau field is a lack of clarity around tau’s normal function in development and disease and how these processes change in the context of causal disease variants or amyloid beta plaques.To address these questions in an unbiased manner, we conducted multi-omic characterization of iPSC-derived neurons harboring the MAPT V337M mutation, which revealed major changes in regulators of axonogenesis. MAPT V337M neurons have increased axon branching. Pathogenic tau mutations have generally been assumed to act through a gain of toxic function, leading to therapeutic approaches aiming to lower tau levels that are currently in clinical trials. Surprisingly, we found that tau knockdown did not rescue axon branching in MAPT V337M neurons, and tau knockdown induced axon branching in MAPT WT neurons, strongly supporting a tau loss of function effect. Intriguingly, knockdown the tau-interacting protein MYO1B also increases axon branching in wild-type neurons without modifying axon branching in MAPT V337M neurons. We conclude that the FTD-associated tau mutation MAPT V337M drives major changes in neuronal differentiation and maturation caused by loss of tau function

iNeuron pre-differentiation & differentiation protocol v2

This protocol describes thedifferentiation of iPSCs with stably integrated doxycycline-inducible Ngn2 (such as i3Ns). </p

iNeuron pre-differentiation &amp; differentiation protocol v1

This protocol describes thedifferentiation of iPSCs with stably integrated doxycycline-inducible Ngn2 (such as i3Ns). </p