PIPages
Labs

Christina Lee

Carnegie Mellon University, PA·Biochemistry

Inside every cell, the endoplasmic reticulum (ER) forms a branching network of membrane tubes where proteins and fats are made. The ER's net-like shape matters for sending proteins to the right places, secreting them, forming lipid droplets and autophagy, the cell's self-recycling process.

Fields

Biochemistry

Biology

Biophysics

Topics

endoplasmic reticulum

ER morphology

membrane fusion

Grants
1 known grant, through Aug 2027

What they work on

  1. Determine how the variable C-terminal tails of human atlastins ATL1 and ATL2 block their own membrane fusion activity, including whether the ATL2 tail inserts into the membrane as a helix, using fusion of purified proteins reconstituted in vitro.
  2. Uncover how this tail-based autoinhibition controls ATL1 and ATL2 fusion activity in different cell types.
  3. Test whether the hereditary spastic paraplegia proteins ATL1, REEP1 and M1-spastin regulate one another as a three-part network that maintains ER structure in neurons, including how REEP1 suppresses fusion and M1-spastin activates it.

More about the research

The network is maintained as tubes grow and then fuse with one another. That fusion is driven by atlastins (ATLs), proteins anchored in the ER membrane that use the energy molecule GTP to merge membranes. Humans have three versions. ATL1 is found mainly in neurons, and its mutations cause hereditary spastic paraplegia (HSP), a disorder in which leg muscles become progressively stiff and weak. Mutations in ATL3 cause hereditary sensory neuropathy, a nerve disorder that affects sensation. ATL2 and ATL3 are found in many tissues.

Why it matters

Hereditary spastic paraplegia is caused by mutations in ATL1 and other genes that shape the ER. Learning how ATL1 is switched on and off, and how it works with REEP1 and M1-spastin, may help explain how these mutations damage neurons. Understanding these mechanisms could eventually inform approaches to this movement disorder and to hereditary sensory neuropathy.

Known grants

From NIH and NSF research grants. Labs often have other funding we can't see.

Mechanism and Role of Membrane Fusion by the Atlastin GTPase

NIH · Aug 2014 – Aug 2027

Closest labs

Geoffrey W Abbott

University of California-Irvine, CA·Pharmacology

Delineate how carnosic acid opens Kv7.3 but not Kv7.2, and how gentisic acid potently opens Kv7.3 and Kv7.2/3, using all-atom molecular dynamics simulations, site-directed mutagenesis and electrophysiology.

Tom A Rapoport

Harvard University, MA·Biochemistry

Determine how misfolded glycoproteins, proteins carrying sugar chains, are delivered to the Hrd1 complex and moved from the ER interior across the membrane, building on cryo-electron microscopy structures.

Gary Bassell

Emory University, GA·Neuroscience

Identify the RNA binding proteins and mRNA cargoes carried by the kinesin motor KIF1C, and test whether SPG58 pathogenic variants alter that binding, using mass spectrometry in CRISPR-generated KIF1C knockout human iPSC-derived motor neurons.

The school

Carnegie Mellon University: 28 labs on PI Pages, $505M a year on research, 346 research doctorates a year.

More about Carnegie Mellon University

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