Biology subjects

Strittmatter, L.

Publications and source records attributed to Strittmatter, L..

3 recordsLinked to original sources

bioRxiv2020

Deficient spermiogenesis in mice lacking Rlim

The X-linked gene Rlim plays major roles in female mouse development and reproduction, where it is crucial for the maintenance of imprinted X chromosome inactivation in extraembryonic tissues of embryos. However, while females carrying a systemic Rlim knockout (KO) die around implantation, male Rlim KO mice appear healthy and are fertile, raising questions as to the pressures driving Rlim gene selection during evolution. Here we report an important role for Rlim in testis where it is highly expressed in post-meiotic round spermatids as well as in Sertoli cells. Systemic deletion of the Rlim gene leads to lower numbers of mature sperm that contains excess cytoplasm, leading to decreased sperm motility and in vitro fertilization rates. Targeting the conditional Rlim cKO specifically to the spermatogenic cell lineage largely recapitulates this phenotype. These results reveal functions of Rlim in male reproduction specifically in round spermatids during spermiogenesis with likely evolutionary implications.

developmental biology↗

bioRxiv2020

UPRmt scales mitochondrial network expansion with protein synthesis via mitochondrial import

As organisms develop, individual cells generate mitochondria to fulfill physiologic requirements. However, it remains unknown how mitochondrial network expansion is scaled to cell growth and impacted by environmental cues. The mitochondrial unfolded protein response (UPRmt) is a signaling pathway mediated by the transcription factor ATFS-1 which harbors a mitochondrial targeting sequence (MTS)1. Here, we demonstrate that ATFS-1 mediates an adaptable mitochondrial expansion program that is active throughout normal development. Developmental mitochondrial network expansion required the relatively inefficient MTS2 in ATFS-1, which allowed the transcription factor to be responsive to parameters that impact protein import capacity of the entire mitochondrial network. Increasing the strength of the ATFS-1 MTS impaired UPRmt activity throughout development due to increased accumulation within mitochondria. The insulin-like signaling-TORC13 and AMPK pathways affected UPRmt activation4,5 in a manner that correlated with protein synthesis. Manipulation to increase protein synthesis caused UPRmt activation. Alternatively, S6 kinase inhibition had the opposite effect due to increased mitochondrial accumulation of ATFS-1. However, ATFS-1 with a dysfunctional MTS6 constitutively increased UPRmt activity independent of TORC1 function. Lastly, expression of a single protein with a strong MTS, was sufficient to expand the muscle cell mitochondrial network in an ATFS-1-dependent manner. We propose that mitochondrial network expansion during development is an emergent property of the synthesis of highly expressed mitochondrial proteins that exclude ATFS-1 from mitochondrial import, causing UPRmt activation. Mitochondrial network expansion is attenuated once ATFS-1 can be imported.

molecular biology↗

bioRxiv2019

A DNA-guided Argonaute Protein Functions in DNA Replication in Thermus thermophilus

Argonaute proteins use nucleic acid guides to protect organisms against transposons and viruses. In the eubacterium Thermus thermophilus, the DNA-guided Argonaute TtAgo defends against transformation by DNA plasmids. Here, we report that TtAgo also participates in DNA replication. TtAgo binds small DNA guides derived from the chromosomal region where replication terminates and associates with proteins known to act in DNA replication. T. thermophilus deploys a single type II topoisomerase, gyrase. When gyrase is inhibited, T. thermophilus relies on TtAgo to complete replication of its circular genome; loss of both gyrase and TtAgo activity produces long filaments that fail to separate into individual bacteria. We propose that the primary role of TtAgo is to help T. thermophilus disentangle the catenated circular chromosomes made by DNA replication. One Sentence SummaryThe DNA-guided Argonaute protein of Thermus thermophilus helps separate daughter chromosomes at the end of DNA replication.

microbiology↗