Sec12p requires Rer1p for sorting to coatomer (COPI)-coated vesicles and retrieval to the ER

International audienceIn Saccharomyces cerevisiae cells lacking the Rer1 protein (Rer1p), the type II transmembrane protein Sec12p fails to be retained in the ER. The transmembrane domain of Sec12p is sufficient to confer Rer1p-dependent ER retention to other membrane proteins. In rer1 mutants a large part of the Sec12-derived proteins can escape to the late Golgi. In contrast, rer3 mutants accumulate Sec12-derived hybrid proteins carrying early Golgi modifications. We found that rer3 mutants harbour unique alleles of the alpha-COP-encoding RET1 gene. ret1 mutants, along with other coatomer mutants, fail to retrieve KKXX-tagged type I transmembrane proteins from the Golgi back to the ER. Surprisingly rer3-11(=ret1-12) mutants do not affect this kind of ER recycling. Pulse-chase experiments using these mutants show that alpha-COP and Rer1p function together in a very early Golgi compartment to initiate the recycling of Sec12p-derived hybrid proteins. Rer1p protein may be directly involved in the retrieval process since it also recycles between the early Golgi and ER in a coatomer (COPI)-dependent manner. Rer1p may act as an adapter coupling the recycling of non-KKXX transmembrane proteins like Sec12p to the coatomer (COPI)-mediated backward traffic.In Saccharomyces cerevisiae cells lacking the Rer1 protein (Rer1p), the type II transmembrane protein Sec12p fails to be retained in the ER. The transmembrane domain of Sec12p is sufficient to confer Rer1p-dependent ER retention to other membrane proteins. In rer1 mutants a large part of the Sec12-derived proteins can escape to the late Golgi. In contrast, rer3 mutants accumulate Sec12-derived hybrid proteins carrying early Golgi modifications. We found that rer3 mutants harbour unique alleles of the alpha-COP-encoding RET1 gene. ret1 mutants, along with other coatomer mutants, fail to retrieve KKXX-tagged type I transmembrane proteins from the Golgi back to the ER. Surprisingly rer3-11(=ret1-12) mutants do not affect this kind of ER recycling. Pulse-chase experiments using these mutants show that alpha-COP and Rer1p function together in a very early Golgi compartment to initiate the recycling of Sec12p-derived hybrid proteins. Rer1p protein may be directly involved in the retrieval process since it also recycles between the early Golgi and ER in a coatomer (COPI)-dependent manner. Rer1p may act as an adapter coupling the recycling of non-KKXX transmembrane proteins like Sec12p to the coatomer (COPI)-mediated backward traffic

Evolution of the endomembrane systems of trypanosomatids:conservation and specialisation

Parasite surfaces support multiple functions required for survival within their hosts, and maintenance and functionality of the surface depends on membrane trafficking. To understand the evolutionary history of trypanosomatid trafficking, where multiple lifestyles and mechanisms of host interactions are known, we examined protein families central to defining intracellular compartments and mediating transport, namely Rabs, SNAREs and RabGAPs, across all available Euglenozoa genomes. Bodonids possess a large trafficking repertoire, which is mainly retained by the Trypanosoma cruzi group, with extensive losses in other lineages, particularly African trypanosomes and phytomonads. There are no large-scale expansions or contractions from an inferred ancestor, excluding direct associations between parasitism or host range. However, we observe stepwise secondary losses within Rab and SNARE cohorts (but not RabGAPs). Major changes are associated with endosomal and late exocytic pathways, consistent with the diversity in surface proteomes between trypanosomatids and mechanisms of interaction with the host. Along with the conserved core family proteins, several lineage-specific members of the Rab (but not SNARE) family were found. Significantly, testing predictions of SNARE complex composition by proteomics confirms generalised retention of function across eukaryotes

Eine Lehrveranstaltung - ein Dokument

In the university course „Tutorium zur Physik“ the physics students of TU Darmstadt must keep a learning journal in Mahara to describe their own expertise development. In the students` opinion Mahara needs an enormous amount of time and it is hard to design the journal. The students journalize at odd times and they don’t describe their development very well. To improve the journals, the motivation and the communication about the course, the teachers established a collaborative learning journal, which is written with the software OneNote by Microsoft, at summer semester 2016. OneNote has more technical compabilities to design the journals and the students can annotate each others journals. In the collaborative learning journal the students merge feelings and thoughts about the learning content. In the individual part they reflect their findings and own development similar to the journals in Mahara

Kollaborative Lerntagebücher im Tutorium zur Physik

In der Lehrveranstaltung Tutorium zur Physik des Fachbereichs Physik der TU Darmstadt führen die Studierenden Lerntagebücher in Mahara über die eigene Lernentwicklung. Die Studierenden nehmen Mahara als zeitaufwändig und in den Gestaltungsmöglichkeiten ein-schränkend war. Deshalb werden die Lerntagebücher unregelmäßig geführt, enthalten nur geringe Reflexionsanteile und es findet kein Austausch zwischen den Teilnehmenden statt. Um den Reflexionsgrad und die Motivation zur Anfertigung der Tagebücher zu steigern, wurde im Sommersemester 2016 statt Mahara die Software OneNote von Microsoft verwendet, die vielfältige Gestaltungs- und Annotationsmöglichkeiten bietet. Zunächst wurde ein kollaboratives Lerntagebuch zum Zusammentragen der Eindrücke, Gedanken und Ideen geführt, um die Kommunikation über die Inhalte der Lehrveranstaltung zu fördern. Die gewonnenen Erkenntnisse wurden anschließend von jedem Teilnehmer in einem individuellen Lerntagebuch reflektiert.In the university course „Tutorium zur Physik“ the physics students of TU Darmstadt must keep a learning journal in Mahara to describe their own expertise development. In the stu-dents` opinion Mahara needs an enormous amount of time and it is hard to design the journal. The students journalize at odd times and they don’t describe their development very well. To improve the journals, the motivation and the communication about the course, the teachers established a collaborative learning journal, which is written with the software OneNote by Microsoft, at summer semester 2016. OneNote has more technical compabilities to design the journals and the students can annotate each others journals. In the collaborative learning journal the students merge feelings and thoughts about the learning content. In the individual part they reflect their findings and own development similar to the journals in Mahara

How personalised medicine will transform healthcare by 2030: the ICPerMed vision

This commentary presents the vision of the International Consortium for Personalised Medicine (ICPerMed) on how personalised medicine (PM) will lead to the next generation of healthcare by 2030. This vision focuses on five perspectives: individual and public engagement, involvement of health professionals, implementation within healthcare systems, health-related data, and the development of sustainable economic models that allow improved therapy, diagnostic and preventive approaches as new healthcare concepts for the benefit of the public. We further identify four pillars representing transversal issues that are crucial for the successful implementation of PM in all perspectives. The implementation of PM will result in more efficient and equitable healthcare, access to modern healthcare methods, and improved control by individuals of their own health data, as well as economic development in the health sector.Funding Agencies|European Unions Horizon 2020 Research and Innovation Programme [731366]</p