MRC National Institute for Medical Research, London
Science for Health
Sila Konur Ultanir group project:
Functions of novel NDR1/2 substrates in neural development
Nuclear Dbf2-related (NDR) family kinases NDR1 and NDR2 are serine/ threonine kinases that are highly conserved from yeast to mammals with important functions in organ size control, cellular morphogenesis and polarized growth. We have recently shown that in rodents NDR1/2 kinases are critical for the development of dendrites as well as dendritic spines and excitatory synapses. Using powerful chemical genetic methods we identified five novel substrates of NDR1 which implicate this signaling pathway as a key regulator of membrane trafficking (Table 1). Furthermore we have shown that two of these novel substrates, AAK1 and Rabin8, function in dendrite and spine development downstream of NDR1 (Figure 2). We now aim to further characterize the expression pattern, localization and functional roles of the remaining three novel NDR1 substrates in the developing brain.
Table 1:
NDR1 Substrate |
Phosphorylation site |
Cellular function |
|
AAK1 (AP2-associated kinase 1) |
HRRILS*D |
S635 |
Endocytosis, receptor recycling |
Rabin8 (Rab3AIP- Rab3A interacting protein) |
HTRNKS*T |
S240 |
Rab8-GEF, secretory vesicle trafficking |
PI4KB (pik4cb, Phosphatidyl inositol 4 kinase beta) |
HQRSKS*D |
S277 |
Membrane lipid composition, trafficking |
Panx2 (Pannexin-2) |
HTRHFS*L |
S514 |
Large pore channel |
Rab11fip5 (Rab11 family interacting protein 5) |
HKRTYS*D |
S307 |
Recycling endosome |
Figure 2
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Summary depicting the role of NDR1 kinase and its substrates AAK1 and Rabin8 in dendrite development.
Membrane trafficking is a highly regulated process involving multiple compartments with signature molecular compositions and regulators. Which steps of vesicle trafficking are regulated by NDR1/2? By incorporating high resolution live-imaging and acute and chronic kinase inhibition strategies, we will investigate trafficking steps affected by NDR1/2 and its downstream effector kinase AAK1 during development and synaptic plasticity inducing paradigms in cultures.
Ultanir group
Recent publications
Research projects
- Functions of novel NDR1/2 substrates in neural development
- Mechanistic understanding of CDKL5 function
Ultanir biography
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