(From left) Chan Choo Yap, PhD, and Bettina Winckler, PhD
Bettina Winckler, PhD, the Harrison Distinguished Teaching Professor of Cell Biology and Chan Choo Yap, PhD, an assistant professor of research in the Winckler Lab, were awarded a $2.8 million NIH grant, titled “Organization and Function of Neuronal Endosomes,” which marks the fourth renewal of this grant now in year 21 of funding.
Since neurons are extraordinarily large and extremely long-lived, the maintenance of the neuronal proteome is particularly challenging. Failure to maintain neuronal protein homeostasis is a defining feature of many neurodegenerative diseases and of aging, and genes linked to endosomal pathways are frequently associated with such diseases. Notably, Rab7 is genetically linked to the peripheral neuropathy Charcot-Marie-Tooth Disease 2B.
The Winckler lab studies the neuronal functions of the endosomal small GTPase Rab7, which regulates the maturation, motility and fusion of late endosomes and lysosomes, and thus controls degradative flux for protein turnover. In addition, signaling of a multitude of endocytosed receptors is determined by the rate with which they reach lysosomes, pointing to a second critical role of Rab7-regulated endosomal transport: setting signal duration of endocytosed receptors, such as the neurotrophins. Uncovering how neurons regulate their endo-lysosomal pathways is thus critical for understanding development, synapse function, aging and neurodegeneration.
Collaborators on the grant are James Casanova, PhD, a professor in the Department of Cell Biology and Chris Deppmann, PhD, a professor in the Department of Biology.
Filed Under: Research