Seminar: Assoc. Prof. Mark Wright

Tetraspanins: key regulators of adhesion and migration in immune cells

Date:
15 October 2014 14:00 hrs. - 15:00 hrs.
Location:
Location see remarks
Title:
Tetraspanins: key regulators of adhesion and migration in immune cells
Speaker(s):

Assoc. Prof. Mark Wright, Dept. of Immunology, Monash University, Melbourne, Australia

 

Host(s):

Dr. Annemiek van Spriel, Dept. of TIL, RIMLS

15-10-2014 14:00:0015-10-2014 15:00:00Europe/AmsterdamTetraspanins: key regulators of adhesion and migration in immune cells  Location see remarksRimlsrimls@radboudumc.nl

Remarks / more information:

Location: Knowledge Square, RIMLS Building, 5th floor, route 278

Wright , MarkTetraspanins are a superfamily of proteins with a critical role in organizing signal-transducing microdomains at the cell surface. I will present data that shows that tetraspanins regulate adhesion and migration in at least 3 different types of immune cell: neutrophils, dendritic cells and lymphocytes. Using intravital microscopy, we show that the tetraspanin CD37 is a key player in the inflammatory cascade, as responses induced by the neutrophil mobilising chemokine CXCL1 are reduced in CD37-/- mice. CD37 regulates neutrophil migration through a molecular and functional interaction with b2 integrins. Super-resolution microscopy shows that CD37 and b2 integrin exist together in clusters, and various parameters of integrin function such as adhesion, endocytosis, and cell spreading are all regulated by CD37. Dendritic cells initiate adaptive cellular immunity by migrating to draining lymph nodes where they present antigen to naive T cells. These two key processes are reciprocally regulated by the closely related tetraspanins CD37 and CD82. CD37 is required for dendritic cell migration and negatively regulates antigen presentation. Conversely, CD82 negatively regulates dendritic cell migration but positively regulates antigen presentation. The molecular mechanisms that underlie these phenomena will be discussed and involve the regulation of cytoskeleton rearrangement.

 

Key Publications:

  • Tetraspanin CD37 contributes to the initiation of cellular immunity by promoting dendritic cell migration. Eur J Immunol. 43: 1208-19, 2013
  • The tetraspanin CD37 orchestrates the α(4)β(1) integrin-Akt signaling axis and supports long-lived plasma cell survival. Sci Signal. 5:ra82, 2012. 
  • A complementary role for the tetraspanins CD37 and Tssc6 in cellular immunity. J Immunol. 185:3158-66, 2010.

 



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