In living cells, proteins rarely act alone but rather interact with each other to perform their function. Hence, proteins associate with their binding partners at the right time and place to form protein complexes, conferring a variety of cellular processes. In my laboratory, our studies are focused on elucidating how multi-specific proteins form a stable complex with each interaction partner and conduct their activity in signaling cascades or multi-protein complexes. Currently, we have two main areas of interest: (1) cellular functions of nuclear transport factors beyond nucleocytoplasmic transport; and (2) molecular mechanisms of γ-tubulin ring complex (γ-TuRC)-mediated microtubule formation.
(1) Cellular functions of nuclear transport factors beyond nucleocytoplasmic transport:
Soluble nuclear transport factors, including Importin-α and -β, facilitate nucleocytoplasmic transport. For nuclear import, importins recognize nuclear localization signals (NLS) carried by cargo molecules to transfer cargoes from one side of the nuclear envelope-embedded nuclear pore complex (NPC) to the other. Apart from mediating nuclear transport, Importin-α and -β may play important roles in regulating many other cellular functions. I established my own research group at IMB in 2015 and we have been using a multidisciplinary approach—combining biochemical, structural, and biophysical methods—to study how nuclear transport factors modulate cellular functions beyond nucleocytoplasmic transport.
(2) Molecular basis of γ-TuRC-facilitated microtubule nucleation:
Error-free cell division depends on the assembly of a bipolar microtubule-based spindle. During spindle assembly, microtubule nucleation spatially and temporally controls de novo microtubule synthesis at different microtubule-organizing centers (MTOCs) (e.g. the centrosome). In addition to controlling microtubule number, microtubule polarity and the dynamic properties of the newly-assembled polymers are also highly regulated within the cell in order to establish the bipolar microtubule array. While great progress has been made in producing a “parts list” (e.g. γ-tubulin ring complex (γ-TuRC) and its attachment factors) for microtubule nucleation, it is still unclear how these components work together to give rise to new microtubules. Hence, our goal is to reveal the molecular basis of γ-tubulin-based microtubule nucleation, particularly focusing on how microtproteins Mzt1 and GCP8 modulate γ-TuRC cellular targeting and –mediated microtubule formation.
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