?Project 2 (Gelfand) The goal of this proposal is to study dynamic interactions of vimentin intermediate filaments with two other components of the cytoskeleton, microtubules and actin microfilaments, as well as interactions of VIF with membrane organelles. We will study how intermediate filaments move along microtubules and identify microtubule motors that power this movement. We will determine biochemical basis of vimentin interactions with microtubule motors and identify molecular mechanisms involved in the regulation of these interactions, such as posttranslational modifications of vimentin. We will also find molecular mechanisms of vimentin interaction with actin microfilaments and their bundles and with components of focal adhesions. We will test if interactions of VIF with focal adhesions affect stability of cell-substrate interactions and how vimentin in focal adhesions modulates cell motility. We will identify molecular linkers between actin and intermediate filaments and study functional implications of this association. We will also find how intermediate filaments invade focal adhesions, which focal adhesion proteins link them in place and how intermediate filaments regulate adhesion turnover. Finally, the role of vimentin filaments in transport of membrane organelles will be investigated using two model systems, mitochondria and pigment organelles (melanosomes) in melanophores, because both of these organelles contain bound PKA and PKA-dependent phosphorylation is likely regulated in concert with intermediate filament dynamics and organelle transport.
| Wu, Pei-Hsun; Aroush, Dikla Raz-Ben; Asnacios, Atef et al. (2018) A comparison of methods to assess cell mechanical properties. Nat Methods 15:491-498 |
| Robert, Amélie; Tian, Peirun; Adam, Stephen A et al. (2018) Kinesin-dependent transport of keratin filaments: a unified mechanism for intermediate filament transport. FASEB J :fj201800604R |
| Li, Wen; Zhang, Liyuan; Ge, Xuehui et al. (2018) Microfluidic fabrication of microparticles for biomedical applications. Chem Soc Rev 47:5646-5683 |
| Wang, Zheng; Divanyan, Alex; Jourd'heuil, Frances L et al. (2018) Vimentin expression is required for the development of EMT-related renal fibrosis following unilateral ureteral obstruction in mice. Am J Physiol Renal Physiol 315:F769-F780 |
| Wang, Liqun; Xia, Jing; Li, Jonathan et al. (2018) Tissue and cellular rigidity and mechanosensitive signaling activation in Alexander disease. Nat Commun 9:1899 |
| Bucki, Robert; Durna?, Bonita; W?tek, Marzena et al. (2018) Targeting polyelectrolyte networks in purulent body fluids to modulate bactericidal properties of some antibiotics. Infect Drug Resist 11:77-86 |
| Guo, Ming; Pegoraro, Adrian F; Mao, Angelo et al. (2017) Cell volume change through water efflux impacts cell stiffness and stem cell fate. Proc Natl Acad Sci U S A 114:E8618-E8627 |
| Prakadan, Sanjay M; Shalek, Alex K; Weitz, David A (2017) Scaling by shrinking: empowering single-cell 'omics' with microfluidic devices. Nat Rev Genet 18:345-361 |
| Costigliola, Nancy; Ding, Liya; Burckhardt, Christoph J et al. (2017) Vimentin fibers orient traction stress. Proc Natl Acad Sci U S A 114:5195-5200 |
| Zaritsky, Assaf; Obolski, Uri; Gan, Zhuo et al. (2017) Decoupling global biases and local interactions between cell biological variables. Elife 6: |
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