HAP1 Is Required for Endocytosis and Signalling of BDNF and Its Receptors in Neurons View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2017-01-12

AUTHORS

Yoon Lim, Linda Lin-Yan Wu, Si Chen, Ying Sun, Swarna Lekha Vijayaraj, Miao Yang, Larisa Bobrovskaya, Damien Keating, Xiao-Jiang Li, Xin-Fu Zhou

ABSTRACT

When BDNF binds to its receptors, TrkB and p75NTR, the BDNF-receptor complex is endocytosed and trafficked to the cell body for downstream signal transduction, which plays a critical role in neuronal functions. Huntingtin-associated protein 1 (HAP1) is involved in trafficking of vesicles intracellularly and also interacts with several membrane proteins including TrkB. Although it has been known that HAP1 has functions in vesicular trafficking and receptor stabilisation, it is not yet established whether HAP1 has a role in BDNF and its receptor endocytosis. In the present study, we found that HAP1 is in an interacting complex with p75NTR, TrkB and BDNF, especially newly endocytosed BDNF. BDNF and TrkB internalisation is abolished in HAP1 knock-out (KO) cortical neurons. TrkB downstream signalling pathways such as ERK, Akt and PLCγ-1 are also impaired in HAP1 KO cortical neurons upon BDNF stimulation. Proliferation of cerebellar granule cells is also impaired in cell culture and cerebellum of HAP1 KO mice. Our findings suggest that HAP1 may play a key role in BDNF and its receptor endocytosis and may promote neuronal survival and proliferation. More... »

PAGES

1815-1830

Identifiers

URI

http://scigraph.springernature.com/pub.10.1007/s12035-016-0379-0

DOI

http://dx.doi.org/10.1007/s12035-016-0379-0

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1025274647

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/28083816


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