University of Rochester
Department of Biology
River Campus Box 270211
Rochester, New York 14627-0211
Hutchison 317 (office)
Hutchison 311 (lab)
(585) 276-3897 (office)
(585) 276-2440 (lab)
Cells are highly dynamic systems, in which many components are in constant flux: molecules, supramolecular complexes, and even entire organelles. Frequently, such trafficking is highly directed in space and carefully controlled in time.
Lipid droplets (yellow) and nuclei (blue) in early Drosophila embryos. The Welte laboratory studies the molecular mechanisms and biological roles of two types of trafficking events: the exchange of proteins between lipid droplets, cytoplasmic storage organelles, and the nucleus, as well as the motor-powered transport of various cargoes along microtubules. We employ Drosophila models in which we can combine in vivo visualization with molecular genetics approaches. We dissect the molecular mechanisms of these trafficking events and determine the consequences of disrupted trafficking at the organismal level. Our research is very visual and generates striking images (see the examples on the lab website). Currently, we are focusing on three general areas: the role of lipid droplets as sequestration sites for nuclear proteins, the mechanism by which Klarsicht modulates motor-driven transport, and the temporal regulation of lipid-droplet motion.
Lipid droplets as protein sequestration sites
The variant histone H2Av (green) is present on lipid droplets and in nuclei. Lipid droplets are critical for lipid metabolism and energy homeostasis. We found that in Drosophila embryos lipid droplets also sequester massive amounts of certain histones (Cermelli et al., 2006), via the novel histone anchor Jabba (Li et al., 2012). Droplet-bound histones can be released, travel to the nuclei, and support chromatin assembly. In addition, droplet-bound histones contribute to a potent anti-bacterial defense mechanism (Anand et al., 2012). These studies revealed that in addition to their role in lipid metabolism lipid droplets also function as sites for regulated protein sequestration (Welte, 2007). For histones, such sequestration is important both for long-term storage (Li et al., 2012) and short-term buffering (Li et al., 2014). We are characterizing how Jabba recruits histones to lipid droplets and how histone release from droplets and their transfer to nuclei is regulated.
Motor regulation via the Klarsicht protein
Klar (green) and DNA (blue) in early Drosophila embryos.
Klarsicht is a Drosophila member of the nesprin family of proteins that play critical roles in linking the cytoskeleton to the nucleoskeleton. Klar has indeed important functions in nuclear positioning, nuclear migration, and chromosome segregation. How it acts mechanistically is poorly understood. We found that Klar also regulates the motor-driven transport of lipid droplets in early embryos (Welte et al., 1998; Guo et al., 2005; Yu et al., 2011) and of certain RNAs during oogenesis (unpublished). We are using these systems to determine how Klar interacts with microtubule motors and how Klar can uniquely control distinct transport processes.
Temporal regulation of lipid-droplet motion
Lipid droplets are motile in many cells, including in early Drosophila embryos. Here, droplets move bidirectionally along
Lipid droplets (yellow) undergo global shifts during embryogenesis. microtubules, powered by the motors kinesin-1 and cytoplasmic dynein (Shubeita et al. 2008; Gross et al., 2000). As embryogenesis proceeds, the balance of kinesin- and dynein-based motion is intricately regulated, causing redistribution of the droplet population as a whole. Temporal regulation is achieved via the Halo protein (Gross et al., 2003), which - directly or indirectly – controls the properties of kinesin-1 on droplets. We are determining the molecular mechanism by which Halo alters kinesin-1 function as well as the pathways that control Halo expression.
- I. Gaspar, Y. V. Yu, S. L. Cotton, D.-H. Kim, A. Ephrussi, M. A. Welte. 2014. Klar ensures thermal robustness of oskar localization by restraining RNP motility. J. Cell Biol. 206: 199-215
- Z. Li, M. Johnson, Z. Ke, L. Chen, M. A. Welte. 2014. Drosophila lipid droplets buffer the H2Av supply to protect early embryonic development. Curr. Biol. 22: 1485-1491
- P. Anand, S. Cermelli, Z. Li, A. Kassan, M. Bosch, R. Sigua, L. Huang, A. J. Ouellette, A. Pol, M. A. Welte, S. P. Gross. 2012. A novel role for lipid droplets in the organismal antibacterial response. eLife 1: e00003
- Z. Li, K. Thiel, P. J. Thul, M. Beller, R. Kühnlein, M. A. Welte. 2012. Lipid droplets control the maternal histone supply of Drosophila embryos. Curr. Biol. 22: 2104-2113
- Bickel, P.E., J.T. Tansey, M.A. Welte. 2009. PAT proteins, an ancient family of lipid droplet proteins that regulate cellular lipid stores. Biochimica et Biophysica Acta 1791:419-440.
- Shubeita, G.T., S.L. Tran, J. Xu, M. Vershinin,S. Cermelli, S.L. Cotton, M.A. Welte, S.P. Gross. 2008. Consequences of motor copy number on the intracellular transport of kinesin-1-driven lipid droplets. Cell 135:1098-1107. This article was highlighted in a Preview in the same issue of Cell.
- 2007. Proteins under new management: lipid droplets deliver. TCB 17:363-369.
- 2006. The lipid-droplet proteome reveals that droplets are a protein storage depot. Curr. Biol. 16:1783-1795.
- 2005. Regulation of lipid-droplet transport by the Perilipin homologue LSD2. Curr. Biol. 15:1266-1275.
- 2004. Bidirectional transport along microtubules. Curr. Biol. 148:R525-R537.
- 2003. A determinant for directionality of organelle transport in Drosophila embryos. Curr. Biol. 13:1660-1668.
- 2002. Coordination of opposite-polarity microtubule motors. J. Cell Biol. 156:715-724.
- 1998. Developmental regulation of vesicle transport in Drosophila embryos: forces and kinetics. Cell 92:547-557.
For a full list of publications, please visit the our lab website.