S.82. Nerve Growth Factor and Its Receptor Promote Growth and Survival of Activated, Effector Memory T Lymphocytes

ABSTRACT The neurotrophin receptor TrkA plays critical roles in the nervous system by recruiting signaling molecules that activate pathways required for the growth and survival of neurons. Here, we report APPL1 as a TrkA-associated protein. APPL1 and TrkA coimmunoprecipitated in sympathetic neurons. We have identified two routes through which this association can occur. APPL1 was isolated as a binding partner for the TrkA-interacting protein GIPC1 from rat brain lysate by mass spectrometry. The PDZ domain of GIPC1 directly engaged the C-terminal sequence of APPL1. This interaction provides a means through which APPL1 may be recruited to TrkA. In addition, the APPL1 PTB domain bound to TrkA, indicating that APPL1 may associate with TrkA independently of GIPC1. Isolation of endosomal fractions by high-resolution centrifugation determined that APPL1, GIPC1, and phosphorylated TrkA are enriched in the same fractions. Reduction of APPL1 or GIPC1 protein levels suppressed nerve growth factor (NGF)-dependent MEK, extracellular signal-regulated kinase, and Akt activation and neurite outgrowth in PC12 cells. Together, these results indicate that GIPC1 and APPL1 play a role in TrkA function and suggest that a population of endosomes bearing a complex of APPL1, GIPC1, and activated TrkA may transmit NGF signals.

Download Full-text

Characterization of the MRC OX40 antigen of activated CD4 positive T lymphocytes--a molecule related to nerve growth factor receptor.

The EMBO Journal ◽

10.1002/j.1460-2075.1990.tb08211.x ◽

1990 ◽

Vol 9 (4) ◽

pp. 1063-1068 ◽

Cited By ~ 270

Author(s):

S. Mallett ◽

S. Fossum ◽

A.N. Barclay

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

T Lymphocytes ◽

Growth Factor Receptor ◽

Nerve Growth Factor Receptor ◽

Nerve Growth

Download Full-text

Microsphere embolism-induced elevation of nerve growth factor level and appearance of nerve growth factor immunoreactivity in activated T-lymphocytes in the rat brain

Journal of Neuroscience Research ◽

10.1002/(sici)1097-4547(19990315)55:6<749::aid-jnr9>3.0.co;2-n ◽

1999 ◽

Vol 55 (6) ◽

pp. 749-761 ◽

Cited By ~ 12

Author(s):

Hideyuki Mizuma ◽

Kaori Takagi ◽

Keiko Miyake ◽

Norio Takagi ◽

Kumi Ishida ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

T Lymphocytes ◽

Rat Brain ◽

Factor Level ◽

Nerve Growth ◽

Nerve Growth Factor Level ◽

Activated T Lymphocytes ◽

Microsphere Embolism

Download Full-text

The myelin oligodendrocyte glycoprotein directly binds nerve growth factor to modulate central axon circuitry

The Journal of Cell Biology ◽

10.1083/jcb.201504106 ◽

2015 ◽

Vol 210 (6) ◽

pp. 891-898 ◽

Cited By ~ 19

Author(s):

H.-Christian von Büdingen ◽

Feng Mei ◽

Ariele Greenfield ◽

Sarah Jahn ◽

Yun-An A. Shen ◽

...

Keyword(s):

Nerve Growth Factor ◽

Growth Factor ◽

Axon Growth ◽

Myelin Oligodendrocyte Glycoprotein ◽

Nerve Growth ◽

Growth And Survival ◽

Nociceptive Neurons ◽

Binding Partner ◽

Pain Pathways ◽

Exact Function

Myelin oligodendrocyte glycoprotein (MOG) is a central nervous system myelin-specific molecule expressed on the outer lamellae of myelin. To date, the exact function of MOG has remained unknown, with MOG knockout mice displaying normal myelin ultrastructure and no apparent specific phenotype. In this paper, we identify nerve growth factor (NGF) as a binding partner for MOG and demonstrate that this interaction is capable of sequestering NGF from TrkA-expressing neurons to modulate axon growth and survival. Deletion of MOG results in aberrant sprouting of nociceptive neurons in the spinal cord. Binding of NGF to MOG may offer widespread implications into mechanisms that underlie pain pathways.

Download Full-text