Cyclin-dependent kinase 5 permits efficient cytoskeletal remodeling--a hypothesis on neuronal migration.

نویسندگان

  • Zhigang Xie
  • Benjamin Adam Samuels
  • Li-Huei Tsai
چکیده

Migration of neurons to their proper position underlies mammalian brain development. To remain on the proper path, a migrating neuron needs to detect various external signals and respond by efficiently remodeling its cytoskeleton. Cyclin-dependent kinase 5 (Cdk5), a member of the cyclin-dependent kinase family, regulates neuronal migration by phosphorylating a number of intracellular substrates. Deficiencies in Cdk5 preferentially cause impairments in radial glia-guided migration, a process that involves complex remodeling of the cytoskeleton, particularly the microtubules. Furthermore, the defined substrates of Cdk5 that are important for migration generally link Cdk5 to the cytoskeleton. Interestingly, none of these phosphorylation events seem to directly control the activity of the substrates. Taken together, these findings support a model in which Cdk5 does not directly control the detection of any specific external signals but instead regulates efficient remodeling of the cytoskeleton through phosphorylation of multiple substrates.

برای دانلود رایگان متن کامل این مقاله و بیش از 32 میلیون مقاله دیگر ابتدا ثبت نام کنید

ثبت نام

اگر عضو سایت هستید لطفا وارد حساب کاربری خود شوید

منابع مشابه

Phosphorylation of Drebrin by Cyclin-Dependent Kinase 5 and Its Role in Neuronal Migration

Cyclin-dependent kinase 5 (Cdk5)-p35 is a proline-directed Ser/Thr kinase which plays a key role in neuronal migration, neurite outgrowth, and spine formation during brain development. Dynamic remodeling of cytoskeletons is required for all of these processes. Cdk5-p35 phosphorylates many cytoskeletal proteins, but it is not fully understood how Cdk5-p35 regulates cytoskeletal reorganization as...

متن کامل

Cdk5-dependent Mst3 phosphorylation and activity regulate neuronal migration through RhoA inhibition.

The radial migration of newborn neurons is critical for the lamination of the cerebral cortex. Proper neuronal migration requires precise and rapid reorganization of the actin and microtubule cytoskeleton. However, the underlying signaling mechanisms controlling cytoskeletal reorganization are not well understood. Here, we show that Mst3, a serine/threonine kinase highly expressed in the develo...

متن کامل

The roles of cyclin-dependent kinase 5 in dendrite and synapse development.

Since the isolation of cyclin-dependent kinase 5 (Cdk5), this proline-directed serine/threonine kinase has been demonstrated as an important regulator of neuronal migration, neuronal survival and synaptic functions. Recently, a number of players implicated in dendrite and synapse development have been identified as Cdk5 substrates. Neurite extension, synapse and spine maturation are all modulat...

متن کامل

Septin Phosphorylation and Neuronal Degeneration; Role of Cyclin Dependent Kinase 5 (Cdk5)

Cellular function is tightly regulated by protein kinases that orchestrate cell signaling events [1]. During cell replication, kinases activated by cyclin family members (Cdks) play an important role in regulating transitions through the cell cycle in most organisms. Cdks are activated upon association with cyclin regulatory subunits coupled to a phosphorylation event at specific activation sit...

متن کامل

Cortical development: Cdk5 gets into sticky situations

Cyclin-dependent kinase 5 (Cdk5) is much more than its name implies; it plays a role in neuronal migration, neurite outgrowth and degeneration. Recent evidence suggests that Cdk5 regulates neuronal adhesion and cytoskeletal dynamics.

متن کامل

ذخیره در منابع من


  با ذخیره ی این منبع در منابع من، دسترسی به آن را برای استفاده های بعدی آسان تر کنید

عنوان ژورنال:
  • Cerebral cortex

دوره 16 Suppl 1  شماره 

صفحات  -

تاریخ انتشار 2006