Connor Rosen Profile picture
Jun 26, 2018 9 tweets 3 min read Read on X
Very cool paper on species-specific fertilization in fish mediated by a single Ly6/uPAR protein, Bouncer. biorxiv.org/content/early/…
Bouncer expressed on oocytes is necessary for fertilization in zebrafish by mediating sperm-egg binding and entry. And, incredibly, oocytes expressing Bouncer from a distantly related fish (medaka) could be fertilized by medeka sperm, but not zebrafish sperm, and form chimeras!
This is super interesting, and the molecular mechanisms will be very interesting to follow up. In particular, what's the sperm receptor for Bouncer (since Bouncer is only required on the oocyte - it's not a homotypic interaction)? How did that pair of proteins co-evolve?
The other very interesting observation is that Bouncer is a GPI-linked protein - so it has no clear signaling capability (complicated mechanisms involving clustering / lipid rafts aside), consistent with the observations that the main action is to mediate sperm-egg binding.
What's super interesting is that this is a not-unique mechanism - GPI-linked proteins acting as regulators of adhesion for survival / mating in a species-specific manner. Self-(species)-recognition may be not through obvious signaling mechanisms, just binding!
Examples include the yeast mating proteins (both a- and alpha-agglutinin), Flo1 (also in yeast) acting as a greenbeard gene sufficient for species-specific flocculation (ncbi.nlm.nih.gov/pubmed/19013280), and csaA in slime mold fruiting body formation (ncbi.nlm.nih.gov/pubmed/12511650).
And the nearest human/mouse homolog of Bouncer, SPACA4, is also a GPI-linked protein (like most Ly6/uPAR family members).
So on top of the extremely exciting findings in this paper, there seems to be a general trend towards species-specific interactions across eukaryotes mediated by GPI-linked proteins - high affinity interactions where binding is the key, not signaling.
Awesome preprint, exciting read, and very cool implications! #ASAPBio #Evolution

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More from @connor_rosen

Sep 25, 2020
Here’s a thread on anti-interferon autoantibodies, viral infections, and human immunology. This is less a covid thread, and more an anti-covid thread, if anything…
Summary: anti-IFN auto-Abs may be reflective of chronic inflammation, and may pre-exist in vulnerable groups at high levels. Presence in severe covid cases may therefore reflect basal immune variation which impacts covid, rather than a special covid-specific phenomenon.
This is prompted based on the new Science paper on autoantibodies against Type I IFNs in severe covid patients (science.sciencemag.org/content/early/…). Basically, ~10% of severe covid patients had high titer anti-IFNa antibodies that were functionally neutralizing.
Read 23 tweets
Jun 2, 2020
The message is very simple. #BlackLivesMatter
I'm grateful that others have put together resources like bit.ly/ANTIRACISMRESO…, which has helped me learn to be better. So You Want To Talk About Race by @IjeomaOluo and How To Be An Antiracist by @DrIbram have been amazing, and I'm looking forward to reading deeper.
I haven't seen a similar central resource for donations, but various recommendations led me to eji.org (Equal Justice initiative, focused on criminal justice reform and education), voterparticipation.org (get people registered to vote)...
Read 5 tweets
Apr 21, 2020
The story about mitochondria being ~10° hotter than the rest of the cell, published @PLOSBiology a couple years ago (journals.plos.org/plosbiology/ar…) got some cool, albeit indirect, support recently @naturemethods#Biophysics #CellBiology
The original paper, which was mainly based on the temperature-dependent fluorescence of a mitochondria-targeting probe, was accompanied by a “Primer” (journals.plos.org/plosbiology/ar…) highlighting potential flaws and implications, a special sort-of-peer-review step by PLOS Biology.
This new awesome resource @naturemethods - nature.com/articles/s4159… - offers some intriguing orthogonal validation. This is a proteome-wide study of protein thermal stability across 13 organisms, conducted using a mass-spec-based approach.
Read 11 tweets
Nov 22, 2019
Super neat story on how cellular quality control impacts the mutational landscape of proteins - beneficial mutations in DHFR during deep mutational scanning are totally altered dependent on cellular QC #Biophysics #Evolution biorxiv.org/content/10.110… Way to go! @KortemmeLab
In an initial DMS experiment on DHFR, there were a large number (25% of all sequences!) of advantageous mutations spread across the whole protein. Reintroduction of QC protein Lon reduced the number of advantageous mutants and lowered average benefit of those mutations
Changes in selection coefficient (the “advantageous-ness”) were most striking at hydrophobic/aromatic residues and buried residues - and these correlate with Tm changes of variants. So Lon seems to be imposing higher standards on DHFR, particularly for destabilizing core mutants
Read 5 tweets
Nov 20, 2019
A couple interesting bits of preliminary data on Langerhans cells and the huLangerin mouse used to study them. Effects of developmental absence of LCs on keratinocytes and T cells, and huLangerin-YFP labels some neurons (check your Cre mice!) #Genetics #Immunology
First - effect of loss of LCs in the huLangerin-DTA mice - biorxiv.org/content/10.110…. Bulk RNA-seq showed changes in keratinocytes and dendritic epidermal T cells, including cell-type specific changes (e.g. loss of IL17 pathway in DETCs).
Unfortunately, underlying data (either gene expression tables or raw RNA-seq data) don’t currently seem available, but hopefully the authors get that up shortly. Will be interesting to look at and prompt some hypotheses about how LCs control homeostasis and development.
Read 5 tweets
Nov 18, 2019
CYTOF analysis of human neutrophils - 7 populations with differing phagocytosis, ROS, and FACS-compatible surface marker phenotypes. Changes in distribution between healthy + melanoma patients. #Immunology #Cancer #Neutrophils biorxiv.org/content/10.110…
Circulating neutrophil precursors, aged neutrophils, and a few populations of mature and immature neutrophils. Melanoma stage correlates with loss of dominant N2 (mature, ROS++, lowly phagocytic), and increase of N5 (immature, non-proliferative, ROS+, lowly phagocytic).
Interesting to note the phagocytosis-SSC staining in Fig4A - big changes in SSC for some populations with zymosan, others not so much - degranulation, different phagosomes…? Similarly, bimodal peaks for ROS production in same populations… Image
Read 4 tweets

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