Jadranka Loncarek, Ph.D.
Laboratory of Protein Dynamics and Signaling
Building 560, Room 12-90
Frederick, MD 21702
The aim of our studies is to understand how the proper number of the centrosomes is maintained in proliferating cells.
A centrosome is a minute cellular organelle present in only two copies per typical cycling animal cell. It is built of stable core structure - a centriole- and amorphous cloud of pericentriolar material. A centrosome organizes cytoplasmic microtubule cytoskeleton during interphase. During mitosis, two centrosomes organize poles of mitotic spindle, facilitating proper chromosome alignment and their segregation between two daughter cells. Thus, the centrosomes stabilize the genome forming a bipolar mitotic spindle. Centrosomes also transform into basal bodies to nucleate the formation of primary cilia. Primary cilium is a sensory organelle indispensable for signaling during development and for the normal functioning of many organs. Centrosome is a versatile and dynamic organelle whose function amends to the cell cycle conditions.
Structural and numerical centrosome abnormalities are the hallmark of most tumors, especially aggressive ones. Likewise, the defects in primary cilium formation have been implicated in numerous human diseases. Understanding the molecular mechanisms that regulate centrosome number and function is a paramount for understanding centrosome- related diseases.
A typical dividing human cell has two centrosomes, containing single or duplicated centriole, depending on the phase of the cell cycle. Each centriole is a nine-fold barrel-shaped structure made of nine microtubule triplets and accompanying proteins. By a, yet unknown mechanism, centrioles organize pericentriolar material and, as a result, the number of centrioles determine the number of centrosomes in the cell. The cell strictly controls the number of centrosomes by coupling the centriole cycle with other cell cycle events, so that each preexisting centriole duplicate precisely once per cell cycle and segregate evenly during mitosis. Centriole amplification has been documented to correlate with a loss of tumor suppressor proteins, with oncogenic virus infections, DNA damage, or with prolonged interphase induced by chemical inhibitors. Molecular mechanisms behind these pathological conditions promoting centriole amplification are poorly understood because the basic knowledge about how is centriole cycle regulated during normal cell cycle are still lacking.
A general question and a long-term goal of our research is to understand how centriole cycle is coordinated with other cell cycle events and how is spatially regulated within a centrosome. We study molecular mechanisms that regulate initiation of centriole formation, their maturation, disengagement, and segregation in various normal and transformed mammalian (mostly human) cells in the culture. Methodologically, we use a multipronged experimental approach and combine state of the art molecular biochemical methods with live- and fixed- high-end microscopy techniques, to reach our research goals.
Job openings: To inquire about potential open positions in the lab, please e-mail a cover letter and CV to Dr Loncarek.
Shukla A, Kong D, Sharma M, Magidson V, Loncarek J. Plk1 relieves centriole block to reduplication by promoting daughter centriole maturation. Nat Commun. 2015;6:8077.
Kim TS, Park JE, Shukla A, Choi S, Murugan RN, Lee JH, Ahn M, Rhee K, Bang JK, Kim BY, Loncarek J, Erikson RL, Lee KS. Hierarchical recruitment of Plk4 and regulation of centriole biogenesis by two centrosomal scaffolds, Cep192 and Cep152. Proc Natl Acad Sci U S A. 2013;110(50):E4849-57.
Loncarek J, Hergert P, Khodjakov A. Centriole reduplication during prolonged interphase requires procentriole maturation governed by Plk1. Curr Biol. 2010;20(14):1277-82.
Loncarek J, Khodjakov A. Ab ovo or de novo? Mechanisms of centriole duplication. Mol Cells. 2009;27(2):135-42.
Loncarek J, Hergert P, Magidson V, Khodjakov A. Control of daughter centriole formation by the pericentriolar material. Nat Cell Biol. 2008;10(3):322-8.
Related Scientific Focus Areas
Molecular Biology and Biochemistry
This page was last updated on October 25th, 2019