Keynote Presentation: Membrane-Cytoskeletal Dynamics in Disease

Cells of the liver and pancreas are highly polarized and well differentiated, contributing to food digestion through the secretion of lipid emulsifying bile, and proteolytic juice into the gut.  Both have sophisticated cytoskeletal membrane trafficking machineries that aid in this secretory process while ensuring the maintenance of apical and basolateral membrane domains.  Unfortunately, these organs can become steatotic (fatty), leading to a variety of different diseases.  Further, as the liver is a central blood filtering organ, it also can become infected by a substantial variety of different pathogens.  Both steatosis and chronic infections are known to lead to cancers of the liver and pancreas that are among the most lethal of all cancers with exceptionally poor prognoses. 

This presentation is divided into three parts that are aimed at providing insights into the membrane trafficking processes that play a key role in diseases and neoplasia of the liver and pancreas.  The focus is the role of the actin cytoskeleton and its interaction with both small regulatory GTPases (Rabs) and the large mechanochemical GTPases (dynamins).  The presentation will cover:  first, cytoskeletal dynamics at the leading edge of invading tumor cells that support metastatic migration, second, identification of a new autophagic process (lipophagy) that acts to degrade lipid droplets in steatotic hepatocytes, and finally, an anti-viral dynamin family member that associates with hepatocyte mitochondria to alter the genome of this organelle.

Key references for this presentation include:
•    The cell biology of the hepatocyte: A membrane trafficking machine.  J. Cell Biol. 2019 Jul 1;218(7):2096-2112. 
•    Dynamin 2 interacts with α-actinin 4 to drive tumor cell invasion. Mol. Biol. Cell. 2020 Mar 15;31(6):439-451. 
•    A novel Rab10-EHBP1-EHD2 complex essential for the autophagic engulfment of lipid droplets.  Sci. Adv. 2016 Dec 16;2(12):e1601470. 
•    The anti-viral dynamin family member MxB participates in mitochondrial integrity. Nat. Commun. 2020 Feb 26;11(1):1048.

Learning Objectives:

1. Analyze one cytoskeletal component of tumor cell metastasis.

2. Defining the basis of hepatocellular steatosis and “lipophagy”.

3. Defining a role for an anti-viral dynamin in mitochondrial integrity.