Notch Signaling

About Notch Signaling

　It is said that we humans are composed of 60 trillion cells. How do these countless cells create a single living organism? The key lies in the transmission of information between cells. Cells communicate with other cells using proteins and chemicals called various signal transducers. This exchange of information allows cells to move, change shape, increase, change properties, and sometimes die, thereby building our bodies and carrying out our vital activities.

　One of the ways in which information is transmitted between cells is Notch signaling, which is responsible for the communication of information between neighboring cells. The Notch signaling is mediated by proteins on the sender side, called Delta and Jagged, and by proteins on the receiver side, called Notch, which play important roles. When the Notch protein on the plasma membrane interacts (physically attaches) with the Delta or Jagged protein on the plasma membrane of a neighboring cell, the intracellular portion of the Notch protein (called NICD) is detached. The detached NICD moves from the plasma membrane into the nucleus. In the nucleus, NICD cooperates with another protein called Suppressor of Hairless (Su(H)) to act on DNA and activate the expression of target genes. As a result, it has been shown that cells that send and receive the signal have different properties. (Figure 1)

It is also known that a protein called Mind Bomb (Mib) is important for Notch signaling because it modifies proteins (attaching another protein called ubiquitin) called ubiquitination to Delta and Jagged. Without Mib protein, Notch signaling would not work properly, and cells that send and receive the signal would have the same properties.

What we are studying in the biochemistry lab and trying to clarify

　Notch signaling is responsible for information transmission between cells, especially regulating changes in cell properties (called cell differentiation). It is widely conserved in various animal species and has been shown to play important roles in various aspects of ontogeny. In particular, Notch signaling is known to play an important role in neuronal differentiation, and it is known that disruption of Notch signaling causes cells that would not normally become neurons to become neurons (Figure 2).

Notch signaling has also been reported to be involved in human oncogenesis and genetic diseases (Alagille syndrome, CADASIL syndrome). 　

However, the

How are the multiple types of Delta, Jagged, and Notch (3 types of Delta, 2 types of Jagged, and 4 types of Notch in humans) used in different ways? What are the differences in the combinations?

How do Delta and Jagged with ubiquitin attached by Mib differ from those without ubiquitin attached?

How is Notch signaling regulated in vivo?

How is Notch signaling regulated on/off in vivo?

　Our laboratory is trying to clarify these questions by using cultured cells and zebrafish as models.