Professor Kang Shen

Howard Hughes Medical Institute (HHMI) Investigator, Stanford University, USA

Title: "Establishing and Maintaining Neuronal Polarity"


Neurons are highly polarized cells that face a fundamental challenge of compartmentalizing a vast and diverse repertoire of proteins in order to function and establish neural circuits. The axon initial segment (AIS) is a specialized domain separating a neuron’s morphologically, biochemically, and functionally distinct axon and dendrite compartments. How the AIS maintains polarity between these compartments remains unclear. Here, we identify a conserved and widespread endocytic clearance mechanism in the AIS that is essential for receptor compartmentalization and neuronal polarity. We find that axonally and dendritically polarized membrane proteins are recognized by endocytic machinery in the AIS, endocytosed, and targeted to late endosomes for degradation. Inhibiting AIS endocytosis causes polarized receptor mislocalization, with subsequent morphological and behavioral deficits. Forcing receptor interaction with the AIS master organizer, ankryinG, prevents receptor endocytosis, causes receptor accumulation in the AIS, and weakens receptor compartmentalization. Therefore, specificity of this pathway is controlled by a balance of interactions with the endocytic machinery and AIS architecture: receptor clearance is promoted by endocytic machinery interaction and inhibited by ankyrinG tethering. Our results reveal an endocytic clearance mechanism in the AIS that is essential for neuronal polarity and identify localized endocytosis as a strategy to achieve stringent compartmentalization.


About Neuroscience Seminars

Neuroscience seminars at the QBI play a major role in the advancement of neuroscience in the Asia-Pacific region. The primary goal of these seminars is to promote excellence in neuroscience through the exchange of ideas, establishing new collaborations and augmenting partnerships already in place.

While seminars in the QBI Auditorium have been suspended due to COVID-19, we will still be holding seminars via Zoom. The days and times of these seminars will vary depending on the time zone of the speaker. Please see each seminar listed below for details. 


Neuroscience Seminars archive 2005-2018