TY - JOUR AB - Muskelin (Mkln1) is implicated in neuronal function, regulating plasma membrane receptor trafficking. However, its influence on intrinsic brain activity and corresponding behavioral processes remains unclear. Here we show that murine Mkln1 knockout causes non-habituating locomotor activity, increased exploratory drive, and decreased locomotor response to amphetamine. Muskelin deficiency impairs social novelty detection while promoting the retention of spatial reference memory and fear extinction recall. This is strongly mirrored in either weaker or stronger resting-state functional connectivity between critical circuits mediating locomotor exploration and cognition. We show that Mkln1 deletion alters dendrite branching and spine structure, coinciding with enhanced AMPAR-mediated synaptic transmission but selective impairment in synaptic potentiation maintenance. We identify muskelin at excitatory synapses and highlight its role in regulating dendritic spine actin stability. Our findings point to aberrant spine actin modulation and changes in glutamatergic synaptic function as critical mechanisms that contribute to the neurobehavioral phenotype arising from Mkln1 ablation. AU - Muhia, Mary W AU - YuanXiang, PingAn AU - Sedlacik, Jan AU - Schwarz, Jürgen R. AU - Heisler, Frank F. AU - Gromova, Kira V. AU - Thies, Edda AU - Breiden, Petra AU - Pechmann, Yvonne AU - Kreutz, Michael R. AU - Kneussel, Matthias ID - 12224 JF - Communications Biology KW - General Agricultural and Biological Sciences KW - General Biochemistry KW - Genetics and Molecular Biology KW - Medicine (miscellaneous) SN - 2399-3642 TI - Muskelin regulates actin-dependent synaptic changes and intrinsic brain activity relevant to behavioral and cognitive processes VL - 5 ER - TY - JOUR AB - A high-resolution structure of trimeric cyanobacterial Photosystem I (PSI) from Thermosynechococcus elongatus was reported as the first atomic model of PSI almost 20 years ago. However, the monomeric PSI structure has not yet been reported despite long-standing interest in its structure and extensive spectroscopic characterization of the loss of red chlorophylls upon monomerization. Here, we describe the structure of monomeric PSI from Thermosynechococcus elongatus BP-1. Comparison with the trimer structure gave detailed insights into monomerization-induced changes in both the central trimerization domain and the peripheral regions of the complex. Monomerization-induced loss of red chlorophylls is assigned to a cluster of chlorophylls adjacent to PsaX. Based on our findings, we propose a role of PsaX in the stabilization of red chlorophylls and that lipids of the surrounding membrane present a major source of thermal energy for uphill excitation energy transfer from red chlorophylls to P700. AU - Çoruh, Mehmet Orkun AU - Frank, Anna AU - Tanaka, Hideaki AU - Kawamoto, Akihiro AU - El-Mohsnawy, Eithar AU - Kato, Takayuki AU - Namba, Keiichi AU - Gerle, Christoph AU - Nowaczyk, Marc M. AU - Kurisu, Genji ID - 10310 IS - 1 JF - Communications Biology KW - general agricultural and biological Sciences KW - general biochemistry KW - genetics and molecular biology KW - medicine (miscellaneous) SN - 2399-3642 TI - Cryo-EM structure of a functional monomeric Photosystem I from Thermosynechococcus elongatus reveals red chlorophyll cluster VL - 4 ER - TY - JOUR AB - Early endosomes, also called sorting endosomes, are known to mature into late endosomesvia the Rab5-mediated endolysosomal trafficking pathway. Thus, early endosome existence isthought to be maintained by the continual fusion of transport vesicles from the plasmamembrane and thetrans-Golgi network (TGN). Here we show instead that endocytosis isdispensable and post-Golgi vesicle transport is crucial for the formation of endosomes andthe subsequent endolysosomal traffic regulated by yeast Rab5 Vps21p. Fittingly, all threeproteins required for endosomal nucleotide exchange on Vps21p arefirst recruited to theTGN before transport to the endosome, namely the GEF Vps9p and the epsin-relatedadaptors Ent3/5p. The TGN recruitment of these components is distinctly controlled, withVps9p appearing to require the Arf1p GTPase, and the Rab11s, Ypt31p/32p. These resultsprovide a different view of endosome formation and identify the TGN as a critical location forregulating progress through the endolysosomal trafficking pathway. AU - Nagano, Makoto AU - Toshima, Junko Y. AU - Siekhaus, Daria E AU - Toshima, Jiro ID - 7097 IS - 1 JF - Communications Biology SN - 2399-3642 TI - Rab5-mediated endosome formation is regulated at the trans-Golgi network VL - 2 ER - TY - JOUR AB - The rate of biological evolution depends on the fixation probability and on the fixation time of new mutants. Intensive research has focused on identifying population structures that augment the fixation probability of advantageous mutants. But these amplifiers of natural selection typically increase fixation time. Here we study population structures that achieve a tradeoff between fixation probability and time. First, we show that no amplifiers can have an asymptotically lower absorption time than the well-mixed population. Then we design population structures that substantially augment the fixation probability with just a minor increase in fixation time. Finally, we show that those structures enable higher effective rate of evolution than the well-mixed population provided that the rate of generating advantageous mutants is relatively low. Our work sheds light on how population structure affects the rate of evolution. Moreover, our structures could be useful for lab-based, medical, or industrial applications of evolutionary optimization. AU - Tkadlec, Josef AU - Pavlogiannis, Andreas AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 7210 JF - Communications Biology SN - 2399-3642 TI - Population structure determines the tradeoff between fixation probability and fixation time VL - 2 ER - TY - JOUR AB - Because of the intrinsic randomness of the evolutionary process, a mutant with a fitness advantage has some chance to be selected but no certainty. Any experiment that searches for advantageous mutants will lose many of them due to random drift. It is therefore of great interest to find population structures that improve the odds of advantageous mutants. Such structures are called amplifiers of natural selection: they increase the probability that advantageous mutants are selected. Arbitrarily strong amplifiers guarantee the selection of advantageous mutants, even for very small fitness advantage. Despite intensive research over the past decade, arbitrarily strong amplifiers have remained rare. Here we show how to construct a large variety of them. Our amplifiers are so simple that they could be useful in biotechnology, when optimizing biological molecules, or as a diagnostic tool, when searching for faster dividing cells or viruses. They could also occur in natural population structures. AU - Pavlogiannis, Andreas AU - Tkadlec, Josef AU - Chatterjee, Krishnendu AU - Nowak, Martin A. ID - 5751 IS - 1 JF - Communications Biology SN - 2399-3642 TI - Construction of arbitrarily strong amplifiers of natural selection using evolutionary graph theory VL - 1 ER -