Kathy Trybus, Ph.D.

Professor

Background

Dr. Kathy Trybus received her Ph.D. in 1981 from the University of Chicago in Biophysics. She next went to Brandeis University and worked in a Structural Biology lab in the Rosenstiel Basic Medical Sciences Research Center. In 1998, Dr. Trybus joined the Department faculty at University of Vermont.

Contact

Office:
HSRF 130
802-656-8750

Lab:
HSRF 133
802-656-4433

Lab Team

Carol Bookwalter
Patty Fagnant
Hailong Lu
James Robblee
Jill MacFarlane

Research Description

A major focus of the laboratory is unconventional myosin V, a processive motor that moves cargo along actin for long distances without dissociating. Two class V myosins from budding yeast (called Myo2p and Myo4p) have captured our interest, since both had been characterized to be non-processive, despite being demonstrated cargo transporters. Using single molecule and biochemical techniques, we recently showed that Myo2p can only move processively when it walks on actin tracks that resemble those found in the cell. In this case, yeast tropomyosin was found to be essential for the motor to move processively -- an elegant demonstration of how the track can affect the motor. Myo4p, a single-headed class V myosin in budding yeast, transports mRNA to the bud tip. We showed that an oligomeric adapter protein that links the motor to the cargo (She2p) recruits two motors to form a processive complex. Addition of mRNA cargo greatly stabilizes the complex, so that only motors with cargo can move processively. We are altering the mRNA cargo to understand why localizing mRNAs have multiple "zipcode" elements. Vertebrate myosin Va undergoes a folded (inactive) to extended (active) conformational transition. We are investigating if cargo binding is sufficient to activate the motor, using myoVa-melanophilin-Rab27a-melanosome as a model system. Another major focus is to understand the molecular mechanisms by which point mutations in smooth muscle actin (ACTA2) lead to vascular disease. These studies are made possible by our ability to express homogeneous wild-type and mutant vertebrate actins in the baculovirus/insect cell expression system. Techniques used to assess defects caused by the mutations include: a TIRF based assay that follows polymerization of single actin filaments in real time, measurement of persistence length to assess structural changes in the filament, and motility assays to quantify how fast smooth muscle myosin can move the actin filaments .

Faculty Highlighted Publications

Cui H, Ali MY, Goyal P, Zhang K, Loh JY, Trybus KM, Solmaz SR. Coiled-coil registry shifts in the F684I mutant of Bicaudal D result in cargo-independent activation of dynein motility. Traffic. 2020 Jul;21(7):463-478. doi: 10.1111/tra.12734. PMID: 32378283; PMCID: PMC7437983.

Tjioe M, Shukla S, Vaidya R, Troitskaia A, Bookwalter CS, Trybus KM, Chemla YR, Selvin PR. Multiple kinesins induce tension for smooth cargo transport. Elife. 2019 Oct 31;8:e50974. doi: 10.7554/eLife.50974. PMID: 31670658; PMCID: PMC6904222.

Lu H, Fagnant PM, Trybus KM. Unusual dynamics of the divergent malaria parasite PfAct1 actin filament. Proc Natl Acad Sci U S A. 2019 Oct 8;116(41):20418-20427. doi: 10.1073/pnas.1906600116. Epub 2019 Sep 23. PMID: 31548388; PMCID: PMC6789906.

Robert-Paganin J, Robblee JP, Auguin D, Blake TCA, Bookwalter CS, Krementsova EB, Moussaoui D, Previs MJ, Jousset G, Baum J, Trybus KM, Houdusse A. Plasmodium myosin A drives parasite invasion by an atypical force generating mechanism. Nat Commun. 2019 Jul 23;10(1):3286. doi: 10.1038/s41467-019-11120-0. PMID: 31337750; PMCID: PMC6650474.

Chaudhary AR, Lu H, Krementsova EB, Bookwalter CS, Trybus KM, Hendricks AG. MAP7 regulates organelle transport by recruiting kinesin-1 to microtubules. J Biol Chem. 2019 Jun 28;294(26):10160-10171. doi: 10.1074/jbc.RA119.008052. Epub 2019 May 13. PMID: 31085585; PMCID: PMC6664170.

Lombardo AT, Nelson SR, Kennedy GG, Trybus KM, Walcott S, Warshaw DM. Myosin Va transport of liposomes in three-dimensional actin networks is modulated by actin filament density, position, and polarity. Proc Natl Acad Sci U S A. 2019 Apr 23;116(17):8326-8335. doi: 10.1073/pnas.1901176116. Epub 2019 Apr 9. PMID: 30967504; PMCID: PMC6486769.

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