[R35] Dissecting the Diverse Roles of Importin α at the Plasma Membrane

Ente: National Institute of General Medical Sciences

Scadenza: 2027-07-31

Importo max: 249.999 EUR

Paese: US

Descrizione

Abstract The localization of proteins, in some cases even a single protein, can have profound effects on a multitude of processes fundamental to cell biology. As an American Cancer Society postdoctoral fellow at UC Berkeley, I discovered a new cell biological pathway that cells utilize to concurrently scale organelle size with cell size. This mechanism is based on the reversible palmitoylation and altered subcellular localization of the nuclear import adapter protein importin α which then acts as a sensor of cell size to coordinate organelle scaling and morphology (Brownlee and Heald, Cell 2019). The objective of this study is to pursue the implications of this newly discovered role for importin α at the plasma membrane. While we have already uncovered a fascinating and translationally significant role for importin α’s reversible membrane localization in regulating organelle size concurrently with cell size, we now have preliminary data in support of several new roles for importin α at the plasma membrane involving a multitude of fundamental cell biological processes. Here, we seek to understand in greater detail how importin α localization is orchestrated and to identify additional signaling and cell structure-regulating proteins whose function is modulated by differential importin α localization. Our long-term goal is to elucidate the roles of reversible importin α membrane association in subcellular organization. Our central hypothesis is that importin α membrane association plays a vital, previously unappreciated role not only in spindle and nuclear morphology, but also in additional cellular processes, such as in spindle positioning, formation and length maintenance of the primary cilium, oligodendrocyte branching, cell motility, neuronal dendrite formation, apical-basal polarity, and actin cytoskeletal organization at the cell cortex. The rationale is that completion of this work will lead to several large-scale projects that will ultimately identify key targets for preventing, diagnosing, and/or treating a wide range of life-threatening diseases. The work we propose here will also develop experimental techniques that will constitute a widely applicable platform for assessing and dissecting the role(s) of any protein(s) at the plasma membrane. Finally, this study will elucidate importin α’s previously undiscovered fundamental role as not only a nuclear import protein but as a plasma membrane anchoring protein for large macromolecular complexes. Istituzione: STATE UNIVERSITY NEW YORK STONY BROOK PI: Christopher William Brownlee Progetto: 3R35GM147569-05S1

Settori: National Institute of General Medical Sciences

Vai al bando originale

Registrati gratis su Bandolo per trovare bandi compatibili con la tua azienda.