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Alenius, Mattias
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Publications (10 of 22) Show all publications
Dzaki, N. & Alenius, M. (2024). A cilia-bound unconventional secretory pathway for Drosophila odorant receptors. BMC Biology, 22(1), Article ID 84.
Open this publication in new window or tab >>A cilia-bound unconventional secretory pathway for Drosophila odorant receptors
2024 (English)In: BMC Biology, E-ISSN 1741-7007, Vol. 22, no 1, article id 84Article in journal (Refereed) Published
Abstract [en]

Background: Post-translational transport is a vital process which ensures that each protein reaches its site of function. Though most do so via an ordered ER-to-Golgi route, an increasing number of proteins are now shown to bypass this conventional secretory pathway.

Results: In the Drosophila olfactory sensory neurons (OSNs), odorant receptors (ORs) are trafficked from the ER towards the cilia. Here, we show that Or22a, a receptor of various esters and alcoholic compounds, reaches the cilia partially through unconventional means. Or22a frequently present as puncta at the somatic cell body exit and within the dendrite prior to the cilia base. These rarely coincide with markers of either the intermediary ER-Golgi-intermediate-compartment (ERGIC) or Golgi structures. ERGIC and Golgi also displayed axonal localization biases, a further indication that at least some measure of OR transport may occur independently of their involvement. Additionally, neither the loss of several COPII genes involved in anterograde trafficking nor ERGIC itself affected puncta formation or Or22a transport to the cilium. Instead, we observed the consistent colocalization of Or22a puncta with Grasp65, the sole Drosophila homolog of mammalian GRASP55/Grh1, a marker of the unconventional pathway. The numbers of both Or22a and Grasp65-positive puncta were furthermore increased upon nutritional starvation, a condition known to enhance Golgi-bypassing secretory activity.

Conclusions: Our results demonstrate an alternative route of Or22a transport, thus expanding the repertoire of unconventional secretion mechanisms in neurons.

Place, publisher, year, edition, pages
BioMed Central (BMC), 2024
Keywords
Drosophila, Grasp65, Odorant receptor, Olfactory sensory neurons, Soma to cilia trafficking, Unconventional secretion
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-223625 (URN)10.1186/s12915-024-01877-2 (DOI)001201816100004 ()38610043 (PubMedID)2-s2.0-85190366017 (Scopus ID)
Funder
Swedish Research Council, 2016–05208The Kempe Foundations, SMK-1764The Kempe Foundations, JCK-3158
Available from: 2024-04-25 Created: 2024-04-25 Last updated: 2024-04-25Bibliographically approved
Zhao, Y., Johansson, E., Duan, J., Han, Z. & Alenius, M. (2023). Fat- and sugar-induced signals regulate sweet and fat taste perception in Drosophila. Cell Reports, 42(11), Article ID 113387.
Open this publication in new window or tab >>Fat- and sugar-induced signals regulate sweet and fat taste perception in Drosophila
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2023 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 42, no 11, article id 113387Article in journal (Refereed) Published
Abstract [en]

In this study, we investigate the interplay between taste perception and macronutrients. While sugar's and protein's self-regulation of taste perception is known, the role of fat remains unclear. We reveal that in Drosophila, fat overconsumption reduces fatty acid taste in favor of sweet perception. Conversely, sugar intake increases fatty acid perception and suppresses sweet taste. Genetic investigations show that the sugar signal, gut-secreted Hedgehog, suppresses sugar taste and enhances fatty acid perception. Fat overconsumption induces unpaired 2 (Upd2) secretion from adipose tissue to the hemolymph. We reveal taste neurons take up Upd2, which triggers Domeless suppression of fatty acid perception. We further show that the downstream JAK/STAT signaling enhances sweet perception and, via Socs36E, fine-tunes Domeless activity and the fatty acid taste perception. Together, our results show that sugar regulates Hedgehog signaling and fat induces Upd2 signaling to balance nutrient intake and to regulate sweet and fat taste perception.

Place, publisher, year, edition, pages
Elsevier, 2023
Keywords
CP: Metabolism, CP: Neuroscience, Dome, Drosophila, Et, fat, Hedgehog signaling, hemolymph, Socs36E, sugar, taste, Upd2 signaling
National Category
Cell and Molecular Biology
Identifiers
urn:nbn:se:umu:diva-216665 (URN)10.1016/j.celrep.2023.113387 (DOI)001112475900001 ()2-s2.0-85175610532 (Scopus ID)
Funder
Swedish Research Council, 2016-05208The Kempe Foundations, SMK-1764The Kempe Foundations, JCK-3158
Available from: 2023-11-27 Created: 2023-11-27 Last updated: 2025-04-24Bibliographically approved
Zhao, Y., Khallaf, M. A., Johansson, E., Dzaki, N., Bhat, S., Alfredsson, J., . . . Alenius, M. (2022). Hedgehog-mediated gut-taste neuron axis controls sweet perception in Drosophila. Nature Communications, 13(1), Article ID 7810.
Open this publication in new window or tab >>Hedgehog-mediated gut-taste neuron axis controls sweet perception in Drosophila
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2022 (English)In: Nature Communications, E-ISSN 2041-1723, Vol. 13, no 1, article id 7810Article in journal (Refereed) Published
Abstract [en]

Dietary composition affects food preference in animals. High sugar intake suppresses sweet sensation from insects to humans, but the molecular basis of this suppression is largely unknown. Here, we reveal that sugar intake in Drosophila induces the gut to express and secrete Hedgehog (Hh) into the circulation. We show that the midgut secreted Hh localize to taste sensilla and suppresses sweet sensation, perception, and preference. We further find that the midgut Hh inhibits Hh signalling in the sweet taste neurons. Our electrophysiology studies demonstrate that the midgut Hh signal also suppresses bitter taste and some odour responses, affecting overall food perception and preference. We further show that the level of sugar intake during a critical window early in life, sets the adult gut Hh expression and sugar perception. Our results together reveal a bottom-up feedback mechanism involving a “gut-taste neuron axis” that regulates food sensation and preference.

Place, publisher, year, edition, pages
Nature Publishing Group, 2022
National Category
Neurosciences
Identifiers
urn:nbn:se:umu:diva-202073 (URN)10.1038/s41467-022-35527-4 (DOI)001079390700012 ()36535958 (PubMedID)2-s2.0-85144256450 (Scopus ID)
Funder
Swedish Research Council, 2016-05208The Kempe Foundations, SMK-1764The Kempe Foundations, JCK-3158
Available from: 2023-01-03 Created: 2023-01-03 Last updated: 2025-04-24Bibliographically approved
Jafari, S. & Alenius, M. (2021). Odor response adaptation in Drosophila: a continuous individualization process. Cell and Tissue Research, 83(1), 143-148
Open this publication in new window or tab >>Odor response adaptation in Drosophila: a continuous individualization process
2021 (English)In: Cell and Tissue Research, ISSN 0302-766X, E-ISSN 1432-0878, Vol. 83, no 1, p. 143-148Article in journal (Refereed) Published
Abstract [en]

Olfactory perception is very individualized in humans and also in Drosophila. The process that individualize olfaction is adaptation that across multiple time scales and mechanisms shape perception and olfactory-guided behaviors. Olfactory adaptation occurs both in the central nervous system and in the periphery. Central adaptation occurs at the level of the circuits that process olfactory inputs from the periphery where it can integrate inputs from other senses, metabolic states, and stress. We will here focus on the periphery and how the fast, slow, and persistent (lifelong) adaptation mechanisms in the olfactory sensory neurons individualize the Drosophila olfactory system.

Place, publisher, year, edition, pages
Springer, 2021
Keywords
Drosophila, Olfactory perception, Odorant
National Category
Biochemistry Molecular Biology
Identifiers
urn:nbn:se:umu:diva-180650 (URN)10.1007/s00441-020-03384-6 (DOI)000611434400002 ()33492517 (PubMedID)2-s2.0-85099259672 (Scopus ID)
Available from: 2021-02-24 Created: 2021-02-24 Last updated: 2025-02-20Bibliographically approved
Jafari, S., Henriksson, J., Yan, H. & Alenius, M. (2021). Stress and odorant receptor feedback during a critical period after hatching regulates olfactory sensory neuron differentiation in Drosophila. PLoS biology, 19(4), Article ID e3001101.
Open this publication in new window or tab >>Stress and odorant receptor feedback during a critical period after hatching regulates olfactory sensory neuron differentiation in Drosophila
2021 (English)In: PLoS biology, ISSN 1544-9173, E-ISSN 1545-7885, Vol. 19, no 4, article id e3001101Article in journal (Refereed) Published
Abstract [en]

Here, we reveal that the regulation of Drosophila odorant receptor (OR) expression during the pupal stage is permissive and imprecise. We found that directly after hatching an OR feedback mechanism both directs and refines OR expression. We demonstrate that, as in mice, dLsd1 and Su(var)3-9 balance heterochromatin formation to direct OR expression. We show that the expressed OR induces dLsd1 and Su(var)3-9 expression, linking OR level and possibly function to OR expression. OR expression refinement shows a restricted duration, suggesting that a gene regulatory critical period brings olfactory sensory neuron differentiation to an end. Consistent with a change in differentiation, stress during the critical period represses dLsd1 and Su(var)3-9 expression and makes the early permissive OR expression permanent. This induced permissive gene regulatory state makes OR expression resilient to stress later in life. Hence, during a critical period OR feedback, similar to in mouse OR selection, defines adult OR expression in Drosophila.

Place, publisher, year, edition, pages
Public Library of Science, 2021
National Category
Cell and Molecular Biology Biochemistry Molecular Biology
Identifiers
urn:nbn:se:umu:diva-182748 (URN)10.1371/JOURNAL.PBIO.3001101 (DOI)000636466700002 ()33793547 (PubMedID)2-s2.0-85104276130 (Scopus ID)
Available from: 2021-05-24 Created: 2021-05-24 Last updated: 2025-02-20Bibliographically approved
Maurya, D. K., Bohm, S. & Alenius, M. (2017). Hedgehog signaling regulates ciliary localization of mouse odorant receptors. Proceedings of the National Academy of Sciences of the United States of America, 114(44), E9386-E9394
Open this publication in new window or tab >>Hedgehog signaling regulates ciliary localization of mouse odorant receptors
2017 (English)In: Proceedings of the National Academy of Sciences of the United States of America, ISSN 0027-8424, E-ISSN 1091-6490, Vol. 114, no 44, p. E9386-E9394Article in journal (Refereed) Published
Abstract [en]

The ciliary localization of odorant receptors (ORs) is evolutionary conserved and essential for olfactory transduction. However, how the transport of ORs is regulated in mammalian olfactory sensory neurons is poorly understood. Here we demonstrate that odorant responsiveness and OR transport is regulated by the Hedgehog pathway. OR transport is inhibited by conditional gene inactivation of the Hedgehog signal mediator Smoothened (Smo) as well as by systemic administration of the Smo inhibitor vismodegib, a clinically used anticancer drug reported to distort smell perception in patients. The ciliary phenotype of Smo inhibition is haploinsufficient, cell autonomous, and correlates with the accumulation of OR-containing putative transport vesicles in the cytosol. The Smo-dependent OR transport route works in parallel with a low basal transport of vesicle containing both ORs and other olfactory transduction components. These findings both define a physio logical function of Hedgehog signaling in olfaction and provide an important evolutionary link between olfaction and the requirement of a ciliary compartment for Hedgehog signaling.

Place, publisher, year, edition, pages
National Academy of Sciences, 2017
Keywords
odorant receptors, Hedgehog pathway, Smoothened, vismodegib, cilia transport
National Category
Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-141992 (URN)10.1073/pnas.1708321114 (DOI)000414127400026 ()29078327 (PubMedID)2-s2.0-85032730617 (Scopus ID)
Available from: 2017-11-22 Created: 2017-11-22 Last updated: 2025-02-07Bibliographically approved
Sanchez, G. M., Alkhori Franzén, L., Hatano, E., Schultz, S., Kuzhandaivel, A., Jafari, S., . . . Alenius, M. (2016). Hedgehog Signaling Regulates the Ciliary Transport of Odorant Receptors in Drosophila. Cell Reports, 14(3), 464-470
Open this publication in new window or tab >>Hedgehog Signaling Regulates the Ciliary Transport of Odorant Receptors in Drosophila
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2016 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 14, no 3, p. 464-470Article in journal (Refereed) Published
Abstract [en]

Hedgehog (Hh) signaling is a key regulatory pathway during development and also has a functional role in mature neurons. Here, we show that Hh signaling regulates the odor response in adult Drosophila olfactory sensory neurons (OSNs). We demonstrate that this is achieved by regulating odorant receptor (OR) transport to and within the primary cilium in OSN neurons. Regulation relies on ciliary localization of the Hh signal transducer Smoothened (Smo). We further demonstrate that the Hh- and Smo-dependent regulation of the kinesin-like protein Cos2 acts in parallel to the intraflagellar transport system (IFT) to localize ORs within the cilium compartment. These findings expand our knowledge of Hh signaling to encompass chemosensory modulation and receptor trafficking.

Place, publisher, year, edition, pages
CELL PRESS, 2016
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-146710 (URN)10.1016/j.celrep.2015.12.059 (DOI)000368701600008 ()26774485 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research [F06-0013]

Available from: 2018-04-18 Created: 2018-04-18 Last updated: 2024-01-17
Jafari, S. & Alenius, M. (2015). Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in Drosophila. PLOS Genetics, 11(3), Article ID e1005051.
Open this publication in new window or tab >>Cis-Regulatory Mechanisms for Robust Olfactory Sensory Neuron Class-restricted Odorant Receptor Gene Expression in Drosophila
2015 (English)In: PLOS Genetics, ISSN 1553-7390, E-ISSN 1553-7404, Vol. 11, no 3, article id e1005051Article in journal (Refereed) Published
Abstract [en]

Odor perception requires that each olfactory sensory neuron (OSN) class continuously express a single odorant receptor (OR) regardless of changes in the environment. However, little is known about the control of the robust, class-specific OR expression involved. Here, we investigate the cis-regulatory mechanisms and components that generate robust and OSN class-specific OR expression in Drosophila. Our results demonstrate that the spatial restriction of expression to a single OSN class is directed by clusters of transcription-factor DNA binding motifs. Our dissection of motif clusters of differing complexity demonstrates that structural components such as motif overlap and motif order integrate transcription factor combinations and chromatin status to form a spatially restricted pattern. We further demonstrate that changes in metabolism or temperature perturb the function of complex clusters. We show that the cooperative regulation between motifs around and within the cluster generates robust, class-specific OR expression.

Place, publisher, year, edition, pages
Public Library of Science, 2015
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-146712 (URN)10.1371/journal.pgen.1005051 (DOI)000352197100039 ()25760344 (PubMedID)
Note

Funding Agencies|Swedish Foundation for Strategic Research [F06-0013]; Swedish Research Council [522-2006-6364 / K2007-66P-20436-01-04]

Available from: 2018-04-18 Created: 2018-04-18 Last updated: 2022-09-13Bibliographically approved
Kuzhandaivel, A., Schultz, S. W., Alkhori, L. & Alenius, M. (2014). Cilia-Mediated Hedgehog Signaling in Drosophila. Cell Reports, 7(3), 672-680
Open this publication in new window or tab >>Cilia-Mediated Hedgehog Signaling in Drosophila
2014 (English)In: Cell Reports, E-ISSN 2211-1247, Vol. 7, no 3, p. 672-680Article in journal (Refereed) Published
Abstract [en]

Cilia mediate Hedgehog (Hh) signaling in vertebrates and Hh deregulation results in several clinical manifestations, such as obesity, cognitive disabilities, developmental malformations, and various cancers. Drosophila cells are nonciliated during development, which has led to the assumption that cilia-mediated Hh signaling is restricted to vertebrates. Here, we identify and characterize a cilia-mediated Hh pathway in Drosophila olfactory sensory neurons. We demonstrate that several fundamental key aspects of the vertebrate cilia pathway, such as ciliary localization of Smoothened and the requirement of the intraflagellar transport system, are present in Drosophila. We show that Cos2 and Fused are required for the ciliary transport of Smoothened and that cilia mediate the expression of the Hh pathway target genes. Taken together, our data demonstrate that Hh signaling in Drosophila can be mediated by two pathways and that the ciliary Hh pathway is conserved from Drosophila to vertebrates.

Place, publisher, year, edition, pages
Elsevier, 2014
National Category
Developmental Biology Cell Biology Genetics and Genomics
Identifiers
urn:nbn:se:umu:diva-146705 (URN)10.1016/j.celrep.2014.03.052 (DOI)000335560900009 ()24768000 (PubMedID)
Note

At the time for thesis presentation publication was in status: Manuscript

Available from: 2018-04-18 Created: 2018-04-18 Last updated: 2025-02-01Bibliographically approved
Öst, A., Lempradl, A., Casas, E., Weigert, M., Tiko, T., Deniz, M., . . . Pospisilik, J. A. (2014). Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity. Cell, 159(6), 1352-1364
Open this publication in new window or tab >>Paternal Diet Defines Offspring Chromatin State and Intergenerational Obesity
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2014 (English)In: Cell, ISSN 0092-8674, E-ISSN 1097-4172, Vol. 159, no 6, p. 1352-1364Article in journal (Refereed) Published
Abstract [en]

The global rise in obesity has revitalized a search for genetic and epigenetic factors underlying the disease. We present a Drosophila model of paternal-diet-induced intergenerational metabolic reprogramming (IGMR) and identify genes required for its encoding in offspring. Intriguingly, we find that as little as 2 days of dietary intervention in fathers elicits obesity in offspring. Paternal sugar acts as a physiological suppressor of variegation, desilencing chromatin-state-defined domains in both mature sperm and in offspring embryos. We identify requirements for H3K9/K27me3-dependent reprogramming of metabolic genes in two distinct germline and zygotic windows. Critically, we find evidence that a similar system may regulate obesity susceptibility and phenotype variation in mice and humans. The findings provide insight into the mechanisms underlying intergenerational metabolic reprogramming and carry profound implications for our understanding of phenotypic variation and evolution.

Place, publisher, year, edition, pages
Elsevier (Cell Press), 2014
National Category
Clinical Medicine
Identifiers
urn:nbn:se:umu:diva-146711 (URN)10.1016/j.cell.2014.11.005 (DOI)000346652900014 ()25480298 (PubMedID)
Note

Funding Agencies|Max-Planck Society; EU (NoE Epigenesys); ERC [281641]; Swedish VR [K2011-78PK-21893-01-2]; SSMF grants; Spanish Ministry grant [BFU2011-30246, RYC-2010-07114]; Marie Curie European Reintegration Grant "Evo-Chromo; IMPPC; Champalimaud Foundation; Human Frontiers Program Project Grant [RGP0022/2012]; Portuguese Foundation for Science and Technology (FCT) grant [PTDC/BIA-BCM/118684/2010]; Foundation for Science and Technology [SFRH/BPD/79325/2011]

Available from: 2018-04-18 Created: 2018-04-18 Last updated: 2018-06-09
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